Home About us Contact
|
Home About us Contact | ||
|
|
||
MTHFR
Terms modified by MTHFR Selected AbstractsThe MTHFR C677T polymorphism confers a high risk for stroke in both homozygous and heterozygous T allele carriers with Type 2 diabetesDIABETIC MEDICINE, Issue 5 2006M. P. Hermans Abstract Objective Individuals with Type 2 diabetes are at increased risk of stroke. Plasma homocysteine (tHcy) is an independent risk factor for cardiovascular (CV) disease. The methylene,tetrahydrofolate reductase (MTHFR) gene polymorphism (thermolabile variant C677T) is associated with CV risk, partly as a result of increased Hcy, especially in homozygous subjects. Aim To relate the occurrence of the MTHFR polymorphism with stroke prevalence by examining allelic frequency and genotype distribution in 165 subjects with Type 2 diabetes studied for the presence of thermolabile C677T MTHFR mutation. Results Mean age was 67.7 years, and tHcy 18.2 µmol/l. T allele frequency was 38.5%. MTHFR genotypes were: normal (CC) 40%; heterozygous (CT) 43%; homozygous (TT) 17%. Serum levels of folic acid and B12 vitamin were within normal limits. Stroke prevalence was 14%. Sixty-four per cent of stroke-free subjects had the normal C allele vs. 46% in stroke subjects. The frequencies of genotypes (CC-CT-TT) were (%): 44-41-15 in stroke-free vs. 17-57-26 in stroke patients. Coronary (CAD) and peripheral artery disease (PAD) were common in all groups, with no differences according to genotypes. Stroke prevalence was markedly higher in genotypes CT and TT (18 and 21%) compared with CC (6%). Mean tHcy levels were higher in TT subjects. Conclusion The allelic frequency of C677T MTHFR mutation in Type 2 diabetes subjects with stroke is markedly different from that of subjects without stroke. Genotypic characteristics suggest that C677T MTHFR mutation confers a higher risk for stroke to both homozygous and heterozygous T allele carriers that cannot be ascribed solely to raised tHcy and/or lower folate status in CT subjects, nor to phenotypic expression of conventional risk factors for stroke. The impact of the MTHFR polymorphism on stroke may result from T allele-linked deleterious effects, or C allele-linked protection. Confirmatory studies are warranted, as this cohort was not randomly selected, and a type 1 error cannot be ruled out. [source] Hyperhomocysteinemia in epileptic patients on new antiepileptic drugsEPILEPSIA, Issue 2 2010Vincenzo Belcastro Summary Purpose:, Older enzyme-inducing antiepileptic drugs (AEDs) may induce supraphysiologic plasma concentrations of total (t) homocysteine (Hcy). The aim of the present study was to investigate the effect of new AEDs on plasma tHcy levels. Methods:, Patients 18,50 years of age, on AEDs monotherapy, with no other known cause of hyper-tHcy were enrolled. Plasma tHcy, folate, vitamin B12, and AEDs levels were determined by standard high-performance liquid chromatography (HPLC) methods. Methylenetetrahydrofolate-reductase (MTHFR) polymorphisms were checked using Puregene genomic DNA purification system (Gentra, Celbio, Italy). A group of healthy volunteers matched for age and sex was taken as control. Results:, Two hundred fifty-nine patients (151 on newer and 108 on older AEDs) and 231 controls were enrolled. Plasma tHcy levels were significantly higher [mean values, standard error (SE) 16.8, 0.4 vs. 9.1, 0.2 ,m; physiologic range 5,13 ,m] and folate lower (6.3, 0.1 vs. 9.3, 0.1 nm; normal > 6.8 nm) in patients compared to controls. Patients treated with oxcarbazepine, topiramate, carbamazepine, and phenobarbital exhibited mean plasma tHcy levels above the physiologic range [mean values (SE) 16 (0.8), 19.1 (0.8), 20.5 (1.0), and 18.5 (1.5) ,m, respectively]. Conversely, normal tHcy concentrations were observed in the lamotrigine and levetiracetam groups [both 11.1 (0.5) ,m]. Discussion:, Oxcarbazepine and topiramate might cause hyper-tHcy, most likely because of the capacity of these agents to induce the hepatic enzymes. Because literature data suggest that hyper-tHcy may contribute to the development of cerebrovascular diseases and brain atrophy, a supplement of folate can be considered in these patients to normalize plasma tHcy. [source] Hyperhomocysteinemia in Children Treated with Antiepileptic Drugs Is Normalized by Folic Acid SupplementationEPILEPSIA, Issue 10 2005Martina Huemer Summary:,Purpose: To assess the prevalence of hyperhomocysteinemia in pediatric patients treated with antiepileptic drugs (AEDs) and to evaluate the effect of folic acid supplementation on plasma total homocysteine (tHcy) concentrations in hyperhomocysteinemic patients. Methods: 123 patients from three regional hospitals participated in the study. Patients with hyperhomocysteinemia were included in a 3-month double-blind randomized trial testing oral folic acid supplementation (1 mg/day) versus placebo. Results: Hyperhomocysteinemia (tHcy >10.4 ,mol/L) was present in 19 of 123 patients. Patients with hyperhomocysteinemia were older (13.7 ± 4 vs. 11.0 ± 3.9 years) and had significantly lower folate and cobalamin concentrations. Multidrug (two or more) AED treatment and duration of therapy correlated significantly with elevated total homocysteine (tHcy) and low folate. In contrast, polymorphisms in the methylene tetrahydrofolate reductase gene (MTHFR 677 C,T, 1298 A,C, 1793 G,A) had no significant impact on tHcy. Nine of 19 patients with hyperhomocysteinemia were randomized to placebo, whereas the remaining 10 patients received folic acid supplementation. Folic acid supplementation resulted in a significant increase of folate and decrease of tHcy, whereas both parameters remained unchanged in the placebo group. Conclusions: Hyperhomocysteinemia is present in 15.5% of children receiving long-term AED treatment. Multidrug treatment and long duration of therapy enhance the risk for hyperhomocysteinemia. Folic acid supplementation significantly reduces tHcy. We recommend assessment of serum folate and plasma tHcy in children receiving AEDs. [source] Methylenetetrahydrofolate reductase gene C677T mutation is related to the defects in the internal elastic lamina of the artery wallEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2002P. Hämelahti Abstract Background The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene leads to C/C, C/T and T/T genotypes, which affect the plasma homocysteine concentration in humans. In mini-pigs, high serum homocysteine levels are associated with defects in the internal elastic lamina (IEL) of the artery wall, which are apparently related to the migration of smooth muscle cells into the intima during atherogenesis. We studied the association between the MTHFR genotypes and the number of gaps in the IEL in the wall of the five major abdominal arteries. Materials and methods The autopsy study included 123 subjects (90 males and 33 females) aged 18,93. For the light microscopy, a 0·5 cm circular segment of the coeliac, the superior mesenteric, the inferior mesenteric and the renal arteries were cut and embedded in paraffin blocks. The circumference of the IEL, the thickness of the intima and the number of the gaps per millimetre in the IEL were measured by MOP 3 image analysis. Results The T-allele carriers (C/T and T/T) of the MTHFR gene had significantly less gaps in the IEL than the subjects with the C/C genotype in the superior mesenteric and in the left renal arteries (2·02 ± 2·25 vs. 2·53 ± 1·89, P < 0·04 and 0·56 ± 1·09 vs. 1·82 ± 2·66, P < 0·02, respectively). The trend was similar for the coeliac and the right renal arteries. Conclusions Our result suggests that MTHFR polymorphism may be involved in the fragmentation of the IEL. [source] BRIEF REPORT: Association between MTHFR 677C-T polymorphism and alcohol dependence according to Lesch and Babor typologyADDICTION BIOLOGY, Issue 4 2009Amine Benyamina ABSTRACT Prior studies have associated 677C-T Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with decreased enzymatic activity and modified homocysteine regulation. This study determines and compares MTHFR 677C-T distribution and examines its consequences on homocysteine metabolism and alcohol dependence in alcoholic patients classified according to the Babor and Lesch typologies. MTHFR TT genotype was more prevalent in AD patients with milder alcohol dependence (Babor type A) and with Lesch type 3, associated with depression. MTHFR TT was also associated with hyperhomocysteinemia. Determining MTHFR 677C-T genotype, folate and vitamin B12 levels could assist physicians in identifying type 3 patients and improve addictions management. [source] Segmental testicular ischaemia: presentation, management and follow-upINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 5 2009D. Gianfrilli Summary Segmental infarction of the testis is a rare event. Less than 40 cases have been reported in the literature and its aetiology remains largely unknown. The diagnosis is challenging and its identification crucial as partial ischaemia is frequently confused with testicular tumours and unnecessarily treated with orchiectomy. The objectives of this study are to: (i) raise awareness of this rare condition, (ii) provide the distinctive clinical and radiological features enabling pre-operative diagnosis, (iii) promote appropriate screening of causative factors and (iv) propose an alternative management approach to avoid surgery and preserve fertility. We describe three cases of partial testicular ischaemia in men presenting with reduced sperm quality. The cases demonstrate the ultrasound and magnetic resonance imaging appearance of testicular ischaemia. The surveillance strategy adopted for these lesions indicates that over 2 years of follow-up, marginal changes in the lesions can occur. Histology revealed that infiltration by stromal cells, leucocytes and macrophages is responsible for the remodelling of these lesions. Screening of risk factors for thromboembolism revealed that all patients carried a methylenetetrahydrofolate reductase 677C,T (MTHFR) mutation in a gene involved in folate metabolism, and either borderline or elevated homocysteine levels. Distinctive features permit the pre-operative diagnosis of segmental testicular ischaemia. There are sufficient data to assert that a surveillance strategy is safe and feasible. We speculate that the defects in folate metabolism may pre-dispose individuals to the development of testicular infarction and infertility. [source] Folate metabolism genes, vegetable intake and renal cancer risk in central EuropeINTERNATIONAL JOURNAL OF CANCER, Issue 8 2008Lee E. Moore Abstract In a multicenter case-control study of renal cell carcinoma (RCC) conducted in central and eastern Europe, we reported a strong inverse association with high vegetable intake and RCC risk. The odds ratio (OR) for high compared to the lowest tertile of vegetable intake was OR = 0.67; (95% confidence interval (CI): 0.53,0.83; p -trend < 0.001). We hypothesized that variation in key folate metabolism genes may modify this association. Common variation in 5 folate metabolism genes (CBS: Ex9+33C > T (rs234706), Ex13 +41C > T (rs1801181), Ex18 ,391 G > A (rs12613); MTHFR: A222V Ex5+79C > T (rs1801133), Ex8,62A > C (rs1801131); MTR: Ex26 20A > G (rs1805087), MTRR: Ex5+136 T > C (rs161870), and TYMS:IVS2,405 C > T (rs502396), Ex8+157 C > T (rs699517), Ex8+227 A > G (rs2790)) were analyzed among 1,097 RCC cases and 1,555 controls genotyped in this study. Having at least 1 variant T allele of MTHFR A222V was associated with higher RCC risk compared to those with 2 common (CC) alleles (OR = 1.44; 95% CI: 1.17,1.77; p = 0.001). After stratification by tertile of vegetable intake, the higher risk associated with the variant genotype was only observed in the low and medium tertiles (p -trend = 0.001), but not among those in the highest tertile (p -interaction = 0.22). The association remained robust after calculation of the false discovery rate (FDR = 0.05). Of the 3 TYMS SNPs examined, only the TYMS IVS2 ,405 C (rs502396) variant was associated with a significantly lower risk compared to the common genotype (OR = 0.73; 95% CI: 0.57,0.93). Vegetable intake modified the association between all 3 TYMS SNPs and RCC risk (p -interaction < 0.04 for all). In summary, these findings suggest that common variation in MTHFR and TYMS genes may be associated with RCC risk, particularly when vegetable intake is low. © 2007 Wiley-Liss, Inc. [source] The thymidylate synthase tandem repeat promoter polymorphism: A predictor for tumor-related survival in neoadjuvant treated locally advanced gastric cancerINTERNATIONAL JOURNAL OF CANCER, Issue 12 2006Katja Ott Abstract We evaluated DNA polymorphisms in the thymidylate synthase (TS) and 5,10- methylene-tetrahydrofolate reductase (MTHFR) genes for an association with response and survival in locally advanced gastric cancer treated with 5-FU based preoperative chemotherapy (CTx). DNA of 238 patients (CTx-group: total n = 135, completely resected (R0) n = 102; without CTx: R0 n = 103) was isolated from blood or from nontumorous tissues. In the CTx-group, genotyping of the tandem repeat and the G/C polymorphism in the triple repeat in the promoter region of the TS gene and of the C677T polymorphism of the MTHFR gene was performed. None of the TS or MTHFR genotypes were associated with histopathological response and only the TS tandem repeat polymorphism was significantly related to survival (all patients n = 135, p = 0.002; R0 resected patients n = 102, p = 0.007; log-rank test). Multivariate analysis revealed ypN (p < 0.001) and the TS tandem repeat polymorphism as independent prognostic factors in the CTx-R0-group (p = 0.003). Analyzing the prognostic significance of the TS polymorphisms in the R0-group without CTx, TS genotypes were not significantly associated with survival. Comparing survival between R0 patients with and without CTx in the respective TS genotype groups of the tandem repeat polymorphism, a significant survival benefit for the patients with CTx was found for the 2rpt/2rpt (n = 49; p = 0.002) and 2rpt/3rpt genotypes (n = 99; p = 0.004), but not for the 3rpt/3rpt genotype (n = 57; p = 0.93). Patients' survival after CTx was associated with the TS tandem repeat polymorphism. CTx did not improve survival of patients with the 3rpt/3rpt genotype. Thus, a different therapy might be more appropriate for these patients. © 2006 Wiley-Liss, Inc. [source] Livedoid vasculopathy and hypercoagulability in a patient with primary Sjögren's syndromeINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 4 2007Raquel Cardoso MD Background, A 31-year-old woman presented with a 5-year history of painful ulcerations, palpable purpura, porcelain-white atrophic scars of the malleolar region and dorsal aspect of the feet, livedo reticularis on the limbs, arthralgia, xerophthalmia, and xerostomia. Methods, Skin biopsy revealed vessel wall hyalinization and thrombosis of the microvasculature with a very scarce dermal inflammatory infiltrate. Biopsy of the oral mucosa showed mononuclear infiltration of an intralobular duct of a salivary gland. Results, Laboratory studies, including autoantibodies and inflammation markers, were normal, except for a positive rheumatoid factor. Coagulation screening revealed C677T methylenetetrahydrofolate reductase (MTHFR) mutation, with a normal serum homocysteine. The patient was treated with oral methylprednisolone (32 mg/day with progressive reduction) and enoxaparin (20 mg/day subcutaneously), with complete ulcer healing within 4 months. Conclusion, Livedoid vasculitis or vasculopathy has not been referred to previously in association with Sjögren's syndrome, but may be associated with other autoimmune disorders and anomalies of coagulation, namely factor V Leiden mutation, protein C deficiency, and MTHFR mutation, associated or not with hyperhomocysteinemia, a condition that seems to confer an increased risk of recurrent arterial and venous thrombosis. We stress the importance of anticoagulant therapy for ulcer healing and for the prevention of other thrombotic events. [source] An investigation of associations between alcohol use disorder and polymorphisms on ALDH2, BDNF, 5-HTTLPR, and MTHFR genes in older Korean menINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2010Sangmoon Shin Abstract Background This study aimed to investigate the association of alcohol use disorder (AUD) with four candidate genes in older Korean men: aldehyde dehydrogenase 2 (ALDH2, 1/2), brain-derived neurotrophic factor (BDNF, val66met), serotonin transporter gene linked polymorphic region (5- HTTLPR, s/l), and methylenetetrahydrofolate reductase (MTHFR, c.677C,>,T). Methods A community sample of 300 men aged 65 or over were categorized into 68 subjects with AUD and 232 controls according to clinical examinations and DSM-IV criteria. Genotype distributions and allele frequencies were compared. Results Men with AUD had significantly higher ALDH2*1 and BDNF met allele frequencies compared to controls (p -values,<,0.05). No significant differences in genotype or allele frequencies were found for 5- HTTLPR or MTHFR (p -values,>,0.3). Conclusions AUD was associated with ALDH2*1 and BDNF met alleles in older Korean men. The first is consistent with previous research and likely to be explained by a protective effect of unpleasant symptoms following alcohol consumption associated with ALDH2*2. The second finding is novel and might be accounted for by BDNF -mediated serotonin or dopamine pathways. However, given the relatively small sample size, the results should be regarded as preliminary and requiring independent replication. Copyright © 2009 John Wiley & Sons, Ltd. [source] Methylenetetrahydrofolate reductase gene and risk of Alzheimer's disease in KoreansINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2008Jae-Min Kim Abstract Background The association between methylenetetrahydrofolate reductase (MTHFR) c.677C,>,T (A222V) polymorphism and Alzheimer's disease (AD) is controversial. The objectives of the study were to investigate the association between MTHFR c.677C,>,T polymorphism and AD in Korean elders and to the extent to which it is modified by the major components of one-carbon metabolism and apolipoprotein E (APOE) genotype. Methods Seven hundred and thirty-two community residents aged 65 or over were clinically assessed for AD. Genotyping was performed for MTHFR c.677C,>,T and APOE; serum levels of folate, vitamin B12, and homocysteine were assayed. Age, gender and education were included as covariates. Results A trend of association between TT genotype of MTHFR c.677C,>,T and AD was found [adjusted OR (95% CI): 1.73 (0.80,3.74)]. The association was significant in the presence of below-median vitamin B12 level [3.66 (1.14,11.71)] and in APOE e4 non-carriers [2.97 (1.00,8.55)] with significant interaction terms, and bordered on significance in the presence of above-median homocysteine level [2.73 (0.94,7.90)]. Conclusions These findings suggest gene-environment and gene-gene interactions on the risk of AD in Koreans. Copyright © 2007 John Wiley & Sons, Ltd. [source] Methylenetetrahydrofolate reductase A1298C genotypes are associated with the risks of acute lymphoblastic leukaemia and chronic myelogenous leukaemia in the Korean populationINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2006M. HUR Summary Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism, DNA methylation and synthesis. We investigated the association between MTHFR polymorphisms and the risks of acute and chronic leukaemias. MTHFR C677T and A1298C were genotyped in 396 Korean individuals using multiplex polymerase chain reaction/restriction fragment-length polymorphism. They were acute lymphoblastic leukaemia (ALL, n = 89), acute myeloid leukaemia (AML, n = 55), biphenotypic acute leukaemia (n = 12), chronic myelogenous leukaemia (CML, n = 40), and normal controls (n = 200). C677T genotypes were not associated with the risk of each disease. A1298C variants, however, significantly decreased the risks of ALL and CML compared with 1298AA. Odds ratios and 95% confidence intervals of 1298AC and 1298AC + CC were 0.53 (0.31,0.93) and 0.54 (0.31,0.93) in ALL, and 0.34 (0.14,0.80) and 0.40 (0.18,0.89) in CML, respectively, compared with 1298AA. These findings demonstrate that the development of ALL and CML is more dependent on folate status, and more susceptible to DNA instability than that of AML. In addition, A1298C rather than C677T may be a more important genetic risk modifier in leukaemogenesis at least in the Korean population. [source] Low Dietary Riboflavin but Not Folate Predicts Increased Fracture Risk in Postmenopausal Women Homozygous for the MTHFR 677 T Allele,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2008Nahid Yazdanpanah Abstract The MTHFR C677T polymorphism is associated with mildly elevated homocysteine levels when folate and/or riboflavin status is low. Furthermore, a mildly elevated homocysteine level is a risk factor for osteoporotic fractures. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T variant on fracture risk in 5035 men and women from the Rotterdam Study. We found that the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women. Introduction: The MTHFR C677T polymorphism is associated with mildly elevated homocysteine (Hcy) levels in the presence of low folate and/or riboflavin status. A mildly elevated Hcy level was recently identified as a modifiable risk factor for osteoporotic fracture. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T polymorphism on BMD and fracture risk. Materials and Methods: We studied 5035 individuals from the Rotterdam Study, ,55 yr of age, who had data available on MTHFR, nutrient intake, and fracture risk. We performed analysis on Hcy levels in a total of 666 individuals, whereas BMD data were present for 4646 individuals (2692women). Results: In the total population, neither the MTHFR C677T polymorphism nor low riboflavin intake was associated with fracture risk and BMD. However, in the lowest quartile of riboflavin intake, female 677- T homozygotes had a 1.8 (95% CI: 1.1-2.9, p = 0.01) times higher risk for incident osteoporotic fractures and a 2.6 (95% CI: 1.3-5.1, p = 0.01) times higher risk for fragility fractures compared with the 677-CC genotype (interaction, p = 0.0002). This effect was not seen for baseline BMD in both men and women. No significant influence was found for dietary folate intake on the association between the MTHFR C677T genotype and fracture risk or BMD. In the lowest quartile of dietary riboflavin intake, T-homozygous individuals (men and women combined) had higher (22.5%) Hcy levels compared with C-homozygotes (mean difference = 3.44 ,M, p = 0. 01; trend, p = 0.02). Conclusions: In this cohort of elderly whites, the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women. [source] Influence of cancer-related gene polymorphisms on clinicopathological features in colorectal cancerJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2008Gen Yoshiya Abstract Background and Aim:, Single nucleotide polymorphisms (SNP) are shown to be related with cancer incidence. It has been reported that CCND1, p21cip1DCC, MTHFR, and EXO1 are related with the risk of malignant neoplasm, but few studies have mentioned the prognosis of the patients. We investigated the SNP of patients and related this to clinicopathological features, including survival rate. Method:, DNA from the tissues of primary colorectal cancer was obtained from surgical resections of 114 patients (68 males and 46 females, 29,83 years). The CCND1 polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and those of other genes were investigated by the TaqMan method. The polymorphisms obtained were statistically analyzed for the relationship with clinicopathological features. Results:, The CG + GG allele was more invasive than the CC allele in histological tumor depth in the DCC codon 201 (P = 0.0086). The 677TT allele in MTHFR had a larger tumor size than the 677CC allele (P = 0.028). In EXO1 P757L polymorphism, patients with the TT allele had a statistically reduced survival rate compared with the other alleles. In CCND1 polymorphisms, we found no statistical significance in clinicopathological features. Conclusions:, From these preliminary data, these polymorphisms would be candidates predicting the clinicopathological features of colorectal cancer, but further more systematic gene analyses are warranted. [source] Homocysteine, the MTHFR 677 C,T polymorphism and family history of premature cardiovascular diseaseJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 3 2009A. Carey Background:, Cardiovascular disease (CVD) is the main cause of premature death in the UK and accounts for 36% of all premature male deaths and 27% of female deaths every year (British Heart Foundation, 2006). Although many risk factors for CVD are known, family history has been identified as being of particular importance in premature CVD (Lloyd-Jones et al., 2004). Recently, it was suggested that an elevated homocysteine (tHcy) may be associated with premature CVD (Homocystiene Studies Collaboration, 2002). The main genetic determinant of tHcy is the common 677 C,T polymorphism, in the enzyme methylenetetrahydrofolate reductase (MTHFR), which is prevalent in approximately 10% of the UK population. Relatively few studies have examined the association between tHcy and premature CVD and hardly any have considered the role of this polymorphism. The aim of this study therefore was to examine the relationships between the MTHFR 677 C,T polymorphism, tHcy and a family history of CVD in patients with established premature CVD. Methods:, An analysis was conducted on medical, lifestyle and family history data collected from patients and age-sex matched controls, recruited through the GENOVIT study in 2003. This case,control study involved n = 404 premature CVD patients and a similar number of age-sex matched controls, all of whom were screened for the TT genotype. A subset of patients (n = 196) and controls (n = 167) provided a blood sample, from which the tHcy concentration was established. Independent sample t -tests were used to determine differences between patients and controls and differences among genotype groups were examined using a one-way analysis of variance, followed by a Tukey's post hoc test. Results:, Plasma tHcy was significantly elevated in patients with a family history of CVD (compared to those without) (P = 0.013). A nonsignificant trend towards higher tHcy (compared to those without) was observed in patients with the TT genotype (P = 0.419). Furthermore, specifically in those with the TT genotype, those with a family history of CVD (compared to those without) showed significantly higher tHcy concentrations (P < 0.005). Those with the TT genotype who smoked had significantly higher tHcy (P < 0.05) than the CC and CT genotypes. Discussion:, The findings presented provide evidence to support an association between the MTHFR 677C,T polymorphism, elevated homocysteine and family history of premature CVD. Given that dietary levels of riboflavin have been shown to lower homocysteine specifically in individuals with the TT genotype (McNulty et al., 2006), these results have implications for the dietary management of premature CVD in those individuals with a genetic predisposition for elevated tHcy. In conclusion, further research in larger cohort numbers, regarding the correlation between family history, tHcy and the MTHFR polymorphism, would be beneficial for establishing their cause and effect relationship. References British Heart Foundation (2006) All Deaths and Deaths Under 75 by Cause and Sex, 2005, England, Wales, Scotland, N Ireland and United Kingdom. Available at http://www.bhf.org.uk/research_health_professionals/resources/heart_statistics.aspx. Homocystine Studies Collaboration (2002) Homocysteine and the risk of ishaemic heart disease and stroke. JAMA288, 2015,2022. Llyod-Jones, D.M., Nam, B.H., D'Agostino, R.B., Levy, D., Murabito, J.M., Wang, T.J., Wilson, P.W. & O'Donnell, C.J. (2004) Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults, a prospective study of parents and offspring. JAMA291, 2204,2211. McNulty, H., Dowey le, R.C., Strain, J.J., Dunne, A., Ward, M., Molloy, A.M., McAnena. L.B., Hughes, J.P., Hannon-Fletcher, M. & Scott, J.M. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism. Circulation113, 74,80. [source] Double inherited thrombophilias and adverse pregnancy outcomes: Fashion or science?JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 5 2010Giovanni Larciprete Abstract Aim:, To determine to what extent double inherited thrombophilias are associated with adverse obstetric complications correlated with fetoplacental insufficiency, such as preeclampsia, hemolytic anemia elevated liver enzymes and low platelet count (HELLP) syndrome, gestational hypertension, fetal growth restriction (FGR), intrauterine death (ID), abruptio placentae and disseminated intravascular coagulopathy. Methods:, Pregnant women coming to delivery were retrospectively divided into two groups: group A (controls) and group B (cases). Patients belonging to group B had one of the following: severe preeclampsia, HELLP syndrome, gestational hypertension, FGR, intrauterine death, abruptio placentae of disseminated intravascular coagulopathy. We detected methylenetetrahydrofolate reductase (MTHFR) A1298C, MTHFR C677T, factor V Leiden, PAI-1, mutant prothrombin G20210A, plasma homocysteine, antithrombin III, protein S and activated protein C resistance. Normal pregnant women or pregnant women with double defects were enrolled in this study. Results:, The combination of MTHFR C677T mutation with PAI-1 (5G/5G) mutation was significantly linked with the occurrence of ID. HELLP syndrome was significantly related to the simultaneous presence of factor VIII and X mutations. The combination of MTHFR C677T with factor VIII mutation and the combination of factor II and V mutations were significantly related to the occurrence of abruptio placentae. We found an association between double isoforms MTHFR mutation and FGR. Conclusion:, It seems that some thrombophilias and a combination of thrombophilic factors carry a greater risk than others for a given adverse outcome. Further studies are needed to check the link between thrombophilic gene mutations and adverse pregnancy outcomes, such as recurrent miscarriages and deep venous thrombosis. [source] ACE and MTHFR gene polymorphisms in unexplained recurrent pregnancy lossJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2008Venkatesan Vettriselvi Abstract Aim:, To assess the association between polymorphisms in angiotensin converting enzyme and methylene tetrahydrofolate reductase genes and recurrent pregnancy loss by a case-control study in South Indian women. Methods:, DNA was extracted from peripheral blood leukocytes of 104 women with Recurrent Pregnancy Loss (RPL) and 120 controls. Genotyping of ACE Insertion Deletion and MTHFR C677T polymorphism were carried out by PCR and PCR-RFLP, respectively. Results:, No statistically significant difference was observed in the distribution of genotypes between cases and controls for ACE and MTHFR polymorphisms. Further, the combination of MTHFR and ACE genotypes failed to reveal an association. Conclusion:, In conclusion, the present study reveals lack of association of MTHFR C677T and ACE I/D polymorphisms in RPL in South Indian women. However, we cannot exclude the possibility that other polymorphisms of ACE and MTHFR genes could be associated with the disease and might be clinically useful as a marker to assess risk for RPL. [source] Plasma Homocysteine, Fasting Insulin, and Androgen Patterns among Women with Polycystic Ovaries and InfertilityJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2001Dr. E. Scott Sills Abstract Objective: To measure plasma homocysteine, androgen, and insulin concentrations in women with normal and polycystic-appearing ovaries in an infertility setting. Methods: Among women referred for infertility evaluation (n = 54), homocysteine, androstenedione, DHEAS, total testosterone, fasting insulin/glucose and methyltetrahydrofolate reductase (MTHFR) polymorphism status (C677T mutation) were studied. Ovaries were examined via transvaginal sonogram by one observer and scored as either normal (n = 18) or polycystic (n = 36). Results: When polycystic ovaries were identified, mean total testosterone was significantly higher than when non-polycystic ovaries were present (p = 0.01), although no measured androgen was outside the normal reference range in either group. Average BMI was higher in the polycystic group, but the difference was not significant (p = 0.10). We observed a trend toward higher mean fasting insulin levels in women with polycystic ovaries, but this increase did not reach statistical significance (p = 0.07). Median plasma homocysteine was identical (7.0 mmol/l) in both populations, and no study subject exceeded the current recommended maximum reference value. Conclusions: In this population, the presence of polycystic ovaries was associated with higher serum androgens (especially total testosterone) although none of the measured androgens were above the normal range. While fasting insulin levels were also higher in this group, median plasma homocysteine levels were similar irrespective of ovarian morphology. Concomitant plasma homocysteine derangements in this population of young, lean patients with polycystic-appearing ovaries seem unlikely. Further studies are needed to clarify the role(s) of homocysteine in human reproductive physiology. [source] MTHFR C677T Polymorphism and Risk of HCC in Patients With Liver Cirrhosis: Role of Male Gender and Alcohol ConsumptionALCOHOLISM, Issue 1 2009Carlo Fabris Background:, A single nucleotide polymorphism (SNP) C677T in the methylenetetrahydrofolate reductase (MTHFR) gene has been identified. The TT or CT genotypes show a marked reduction of the enzyme activity; this causes higher homocysteine levels and alterations of folate metabolism. Folate metabolism is essential for DNA synthesis and methylation, crucial steps in carcinogenesis. In this paper, we investigated whether the MTHFR C677T SNP could influence the occurrence of hepatocellular carcinoma (HCC) in a cohort of patients transplanted for end stage liver disease of different etiologies. Methods:, Two hundred and twelve consecutive patients who underwent liver transplantation for end stage liver disease due to hepatitis B or C, alcoholic liver disease, and other causes were studied. Two hundred and thirty-six blood donors served as controls. Focal hepatic lesions were searched in the sectioned explanted livers. The presence of the MTHFR C677T SNP was determined via polymerase chain reaction amplification. Results:, Among the 65 patients with HCC, 22 had the CC genotype, 30 the CT, and 13 the TT genotype. Only in patients with alcoholic liver disease was a significant association detected between the TT genotype and the presence of liver cancer (6/17 vs. 5/46, p < 0.05). At stepwise logistic regression analysis the independent selected predictors of HCC were found: age at transplantation >55 years (p < 0.001) and the association among male gender, alcoholic liver disease, and MTHFR TT genotype (p = 0.002). Conclusions:, The present study suggests that male TT carriers with alcoholic cirrhosis bear an increased risk of developing HCC. [source] Hyperhomocysteinemia and low B vitamin levels are independently associated with venous thromboembolism: results from the EDITH study: a hospital-based case,control studyJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2006E. OGER Summary.,Background:,Moderate hyperhomocysteinemia and B vitamins deficiency are thought to be risk factors for venous thromboembolism (VTE). The causality and independence of those associations are still questioned. Methods:,We measured fasting serum total homocysteine, folates, and vitamin B12 levels as well as 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T genotypes in 467 patients hospitalized with a first well-documented deep vein thrombosis and/or pulmonary embolism not related to a major acquired risk factor and 467 controls matched for gender and age. Results:,Mild hyperhomocysteinemia, low serum folates, and vitamin B12 were associated with VTE independently of each other. In multivariate analysis, odds ratios (OR) (95% CI) for VTE associated with mild hyperhomocysteinemia (>15 ,mol L,1), low serum folates (,,4.9 nmol L,1), and vitamin B12 (, 253 pmol L,1) were 1.48 (1.05,2.08), 3.14 (1.35,7.32) and 1.42 (1.03,1.98), respectively. An MTHFRC677T genotype was not significantly associated with VTE; OR (95% CI): 1.13 (0.70,1.81) Conclusions:,The current data provides further knowledge in the complex relationship between hyperhomocysteinemia, low vitamin levels, and VTE. [source] Impact of environmental and hereditary risk factors on the clinical manifestation of thrombophilia in homozygous carriers of factor V:G1691AJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2004S. Ehrenforth Summary.,Background:,Limited data exist on the clinical manifestations of homozygous factor (F)V:G1691A mutation (FV Leiden) and the impact of environmental and genetic risk factors. Objectives:,To assess the contribution of these factors on the thrombophilic phenotype. Patients and methods:,In a retrospective multicenter cohort study 165 individuals with homozygous FV:G1691A mutation, of whom 129 had previous venous thromboembolism (VTE), were included. To study the role of environmental risk factors, patients were compared by the use of a standardized questionnaire to 165 sex- and age-matched individuals (reference group A); of these, two had previous VTE. To assess the role of genetic risk factors, factor (F)II:G20210A and MTHFR:C677T were determined in individuals homozygous for FV:G1691A and in 177 healthy individuals without previous VTE (reference group B). Results:,The first VTE occurred significantly earlier in women (median age 25 years) than men (35.5 years). In 81% of women and 29% of men an environmental risk factor was present before first VTE. Oral contraceptives increased the risk of thrombosis 4-fold [odds ratio (OR) 4.0, 95% confidence interval (CI) 1.7, 10.4] in women with homozygous FV:G1691A. Postoperative and post-traumatic VTE as first manifestation occurred in 13% and 15% of surgical/traumatic events in patients and in 0.7% and 1.8% in reference group A, respectively (OR 19.7, 95% CI 2.5, 154 and OR 9.2, 95% CI 1.1, 79.4). Heterozygous FII:G20210A was more prevalent in symptomatic patients (11.7%) compared with reference group B (2.8%, OR 4.6, 95% CI 1.6, 13.2). The prevalence of homozygous MTHFR:C677T genotype was similar in patients and reference group B. Conclusions:,Our study supports the concept of thrombophilia as a multifactorial disorder. The knowledge of coexisting factors predisposing to VTE is useful for medical advice for primary and secondary prophylaxis in these patients. [source] Homocysteine levels and sustained virological response to pegylated-interferon ,2b plus ribavirin therapy for chronic hepatitis C: a prospective studyLIVER INTERNATIONAL, Issue 2 2009Guglielmo Borgia Abstract Background: Chronic hepatitis C affects about 3% of the world's population. Pegylated interferon (IFN) , plus ribavirin is the gold standard treatment. Methylenetetrahydrofolate reductase(MTHFR) is a key enzyme in the metabolism of homocysteine. MTHFR gene polymorphisms and high levels of homocysteine are associated with a high degree of steatosis and fibrosis, conditions associated with a low sustained virological response (SVR) rate. Aims: To evaluate whether MTHFR polymorphisms and homocysteine levels are predictors of the outcome of treatment in 102 prospectively enrolled patients with chronic hepatitis C naive to treatment. Methods: Patients were treated with pegylated interferon ,-2b plus ribavirin. All patients underwent blood tests, assessment of homocysteine, vitamin B12, folate, hepatitis C virus (HCV)-RNA levels, screening for MTHFR gene polymorphisms and liver ultrasound examination. Results: Homocysteine levels were deranged (>16 ,mol/L) in 10.5% of MTHFR wild-type patients vs 40.3% of non-wild-type patients (P=0.015). Homocysteine levels were 14.4 ,mol/L in SVR patients and 15.5 ,mol/L in non-SVR patients (P=0.049). The SVR rate was 40.0% in MTHFR wild-type patients, 52.0% in heterozygote mutants and 39.3% in homozygote mutants (P=0.467). At logistic regression analysis, genotypes 2 and 3 (odds ratio: 12.328, 95% confidence interval: 3.390,44.837, P=0.0001), homocysteine <16 ,mol/L (odds ratio: 3.397, 95% confidence interval: 1.033,11.177, P=0.044) and aspartate aminotransferase (AST) levels <48 U/L (odds ratio: 3.262, 95% confidence interval: 1.125,9.458, P=0.029) were independent predictors of SVR. Conclusions: In patients with chronic hepatitis C, homocysteine levels are associated with the outcome of pegylated-IFN, plus ribavirin treatment, while polymorphisms of MTHFR are not. [source] G1793A polymorphisms in the methyl- enetetrahydrofolate gene: Effect of folic acid on homocysteine levelsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 8 2006Sandra Soares Melo Abstract Mutations or polymorphisms in the gene of the enzyme methylenetetrahydrofolate (MTHFR) are associated with hyperhomocysteinemia and possibly with an elevated risk for vascular diseases. A study was conducted on 83 individuals with type 2 diabetes in order to determine the allelic and genotypic frequencies of the G1793A mutation and to assess the effect of folic acid supplementation on plasma homocysteine concentrations. The patients were attended by the Diabetes and Hypertension Program , Balneario Camboriu/SC and received daily supplements containing 1 mg of folic acid for 3 months. DNA was previously extracted from leukocytes and the G1793A mutation was detected by PCR-RFLP. Blood samples were collected during the basal period and after supplementation for the determination of homocysteine by HPLC, and of folic acid and vitamin B12 by RIA. The allele frequency for the G1793A mutation was 3.01% and no homozygous individuals with mutant alleles were detected. Hyperhomocysteinemia was diagnosed in 27.71% of the patients, folic acid deficiency in 15.66%, and vitamin B12 deficiency in 7.23%. Plasma homocysteine concentrations were inversely correlated with folic acid (r = ,0.27, p = 0.01) and vitamin B12 (r = ,0.21; p = 0.05) concentrations. The individuals with a heterozygous genotype for the G1793A mutation showed borderlines or deficient values in folic acid and vitamin B12 concentrations compared to individuals with a normal genotype. Hyperhomocysteinemia and the vitamin deficiencies presented by type 2 diabetic individuals, included with a heterozygous genotype for the G1793A mutation in the MTHFR gene, reached normal values by daily folic acid supplementation. [source] Methylenetetrahydrofolate Reductase Polymorphisms, Folate, and Cancer Risk: A Paradigm of Gene-Nutrient Interactions in CarcinogenesisNUTRITION REVIEWS, Issue 7 2000F.R.C.P.(C), Young-In Kim M.D. Recent epidemiologic studies suggest that common polymorphisms of methylenetetrahydrofolate reductase (MTHFR) with allele frequencies up to 35% in the general North American population may modulate cancer risk. In some cancers, folate and other nutrients involved in the MTHFR metabolic pathway appear to interact with MTHFR polymorphisms to further modify cancer risk. In carcinogenesis, MTHFR polymorphisms thus provide a paradigm of gene-nutrient interactions, an emerging and important topic in the field ofnutritisn and cancer. Furthermore, MTHFR polymorphisms and MTHFR-nutrient interactions provide an opportunity to identify an ideal target group of individuals, at high risk of developing cancer, for rational, effective, and safe chemoprevention using these nutrients. [source] Methylenetetrahydrofolate reductase and methionine synthase reductase gene polymorphisms and protection from microvascular complications in adolescents with type 1 diabetesPEDIATRIC DIABETES, Issue 4pt2 2008Esko J Wiltshire Abstract:, Folate status has been associated with endothelial dysfunction in adolescents with type 1 diabetes, and elevated total plasma homoocyst(e)ine (tHcy) is a risk for vascular disease in the non-diabetic population. Polymorphisms in genes involved in folate and homocysteine metabolism are implicated in vascular disease. We aimed to determine whether polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes are risk factors for early microvascular disease in a large group of adolescents with type 1 diabetes. Four hundred and eighty adolescents were screened annually for retinopathy and microalbuminuria for a median of 4 yr. Molecular analysis for the polymorphisms 677C,T, 1298A,C in MTHFR, and 66A,G in MTRR was performed. The MTRR 66GG genotype reduced the risk for elevated albumin excretion rate (AER) (OR 0.47, CI 0.25, 0.88, p = 0.018) and showed a trend to reduced risk for microalbuminuria (OR 0.27, CI 0.06,1.21, p = 0.09). Survival without elevated AER was increased with the MTRR 66GG genotype (12.4 vs. 9.7 yr, p = 0.04) and with the MTHFR 1298CC genotype (15.2 vs. 10.2 yr, p = 0.007). Conversely, survival without retinopathy was reduced with the MTHFR 677TT and MTRR 66GG combined genotype (6.2 vs. 10.2 yr, p = 0.015). The MTRR 66GG and MTHFR 1298 CC genotypes may confer protection against early nephropathy, possibly because they are associated with lower tHcy. The MTHFR 677 TT was only related to earlier onset retinopathy in combination with MTRR 66GG. [source] Methylenetetrahydrofolate reductase polymorphism in Kawasaki diseasePEDIATRICS INTERNATIONAL, Issue 3 2000Hirokazu Tsukahara Abstract Background: A genetic aberration in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (677 C to T substitution) has been shown to result in reduced enzyme activity. The hypothesis tested in the present study was that a higher proportion of Kawasaki disease (KD) patients with coronary artery lesions (CAL) would have the T677 allele compared with patients without CAL and healthy subjects. Methods: Genotypes for MTHFR were determined in 75 KD patients (male : female ratio 52:23) and 238 healthy subjects (male : female ratio, 110:128) by the polymerase chain reaction and restriction fragment length polymorphism method. Results: The results indicated that female KD patients had a significantly higher frequency of the TT genotype compared with female control subjects. In the female population, the frequency of the TT genotype in patients with initial coronary aneurysm was significantly lower than in patients without this manifestation. Analysis of the data for the male population showed that the frequency of the TT genotype in KD patients developing coronary stenosis, occlusion or myocardial infarction was higher than that in those without these manifestations, although the difference was statistically insignificant. Conclusions: The TT genotype may protect female KD patients against initial aneurysm formation and predispose male KD patients to severe coronary complications. Further large-scale studies may be required to confirm the contribution of homocysteine in the coronary sequelae of KD. [source] C677T polymorphism of methylenetetrahydrofolate reductase gene affects plasma homocysteine level and is a genetic factor of late-onset Alzheimer's diseasePSYCHOGERIATRICS, Issue 1 2004Tomoyuki KIDA Abstract Background:, Elevated plasma homocysteine levels are known as a risk for atherosclerotic vascular disease and venous thrombosis and have been shown as a risk for late-onset Alzheimer's disease (LOAD). Method:, To examine the effect of genetic factors predisposing to elevated plasma homocysteine levels on the occurrence of LOAD, we determined the genotype of a C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene and a variable number tandem repeat (VNTR) spanning exon 13,intron 13 boundary of cystathionine ,-synthase (CBS) gene in patients with LOAD and community-based control subjects. Results:, Logistic regression indicated that the MTHFR-T allele was a risk for LOAD (P < 0.05), independently from apolipoprotein E-,4 (APOE-,4) allele. Kaplan,Meier tests showed that in APOE-,4 non-carriers, individuals with the MTHFR-TT genotype have occurences of LOAD earlier than those with the MTHFR-CC genotype (P < 0.05). Multiple regression analysis indicates that MTHFR-T allele increases plasma homocysteine levels (P = 0.0002), while the number of X chromosomes decreases (P = 0.01). Plasma homocysteine level was not correlated with age, plasma albumin reflecting nutritional condition, and the dose of APOE-,4 allele. The CBS-20 VNTR allele showed the same trend to increase plasma homocysteine level as the MTHFR-T allele, but a risk effect for LOAD was not evident. Conclusion:, A genetic propensity for elevated plasma homocysteine levels, explained by the MTHFR-T allele encoding defective enzymatic function, is involved in the development of LOAD, particularly in APOE-,4 non-carriers, and that homocysteine metabolism could be a preventive target to LOAD in the elderly. [source] Which Thrombophilic Gene Mutations are Risk Factors for Recurrent Pregnancy Loss?AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2006Cyle S. Goodman Problem, Thrombophilia has been associated with poor obstetrical outcomes. To determine the association of specific inherited thrombophilias and recurrent pregnancy loss, 10 thrombophilic genes were investigated. Method of study, A total of 550 women with a history of recurrent pregnancy loss had buccal swabs taken for DNA analyses of the following gene mutations: factor V G1691A, factor V H1299R (R2), factor V Y1702C, factor II prothrombin G20210A, factor XIII V34L, , -fibrinogen -455G>A, PAI-1 4G/5G, HPA1 a/b(L33P), methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C. The frequencies of these mutations were compared with controls published in the literature. Results, When examined individually, PAI-1 4G/5G (P = 0.009), factor XIII V34L (P < 0.0001), and homozygous MTHFR C667T (P < 0.0001) correlated significantly with recurrent pregnancy loss compared with controls. The frequency of the factor V Y1702C mutation was extremely low in patients and controls; thus, this gene was removed from further calculations. The remaining six mutated genes, when analyzed cumulatively, also corresponded with recurrent pregnancy loss (P < 0.0001). Conclusion, A panel of thrombogenic gene mutations consisting of factor V G1691A, factor V H1299R (R2), factor II prothrombin G20210A, factor XIII V34L, , -fibrinogen -455G>A, PAI-1 4G/5G, HPA1 a/b(L33P), MTHFR C677T, and MTHFR A1298C can identify individuals at risk for recurrent pregnancy loss. [source] Association of the C677T polymorphism in the methylenetetrahydrofolate reductase gene with sudden sensorineural hearing loss,,§THE LARYNGOSCOPE, Issue 4 2010Yasue Uchida MD Abstract Objectives/Hypothesis: To investigate the recently reported association of the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene with sudden sensorineural hearing loss (SSNHL), we analyzed data from a community-based Japanese population. Study Design: Nested case-control study. Methods: Among 2,174 adults (1,096 males and 1,078 females) aged 40 to 79 years old who participated in the National Institute for Longevity Sciences,Longitudinal Study of Aging, we compared 33 cases of prevalent SSNHL, defined as a self-reported otolaryngologist diagnosis, with the other cases. Multiple logistic regression was used to obtain odds ratios (ORs) for SSNHL in subjects with the MTHFR C677T polymorphism, with adjustment for other possibly influential factors under additive, dominant, and recessive genetic models. Results: The per-allele ORs for SSNHL risk were 1.687 (95% confidence interval [CI], 1.023,2.780) in model 1, with adjustment for age and sex, and 1.654 (CI, 1.003,2.728) in model 2, with adjustment for smoking status, body mass index, histories of heart disease, hypertension, and diabetes, in addition to the factors in model 1. In model 3, a significant association between SSNHL and the C677T polymorphism was observed under all genetic models independent of factors including folic acid and homocysteine, although there were only 25 cases and 1,677 controls due to the addition of moderating factors. Conclusions: Our results suggest that the T allele of MTHFR C677T could be associated with susceptibility to SSNHL, and even imply that this mutation could be a risk factor that is independent of blood folic acid and homocysteine. Laryngoscope, 2010 [source] Thrombophilic Gene Mutations and Recurrent Spontaneous Abortion: Prothrombin Mutation Increases the Risk in the First TrimesterAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2001Rudolf Pihusch PROBLEM: Thrombophilic predisposition may be one of the underlying causes of recurrent spontaneous abortions (RSA). We studied the prevalence of five thrombophilic gene mutations in patients with RSA. METHOD OF STUDY: 102 patients with two or more consecutive abortions and 128 women without miscarriage were analyzed for factor V Leiden mutation (FVL), prothrombin G20210A mutation (PTM), C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, glycoprotein IIIa (GPIIIa) C1565T polymorphism, and ,-fibrinogen G-455A polymorphism by polymerase chain reaction (PCR) techniques. RESULTS: No differences in the prevalence of FVL, MTHFR T/T, GPIIIa and ,-fibrinogen polymorphism were detected. Heterozygous PTM occurred more often in patients with RSA. This effect was significant in a subgroup with abortions exclusively in the first trimester (6.7% vs. 0.8%, P=0.027, OR 8.5). CONCLUSIONS: In contrast to the other mutations and polymorphisms, heterozygous PTM is more common in patients with abortions in the first trimester. This might reflect an influence of PTM on pathogenesis of early pregnancy loss. [source] | |||||||||||||||||||||||||||||||