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C Polymorphism (c + polymorphism)
Selected AbstractsThe +869T/C polymorphism in the transforming growth factor-,1 gene is associated with the severity and intractability of autoimmune thyroid diseaseCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2008H. Yamada Summary The severity of Hashimoto's disease (HD) and the intractability of Graves' disease (GD) vary among patients. To clarify whether the +869T/C polymorphism in the transforming growth factor-,1 (TGF-,1) gene, which is associated with TGF-,1 expression, is involved in the intractability of GD and severity of HD, we genotyped the TGF-,1 +869T/C polymorphism by polymerase chain reaction,restriction fragment length polymorphism method in genomic DNA samples from 33 patients with HD who developed hypothyroidism before they were 50 years old (severe HD) and 30 untreated, euthyroid patients with HD who were older than 50 years (mild HD). We also examined 48 euthyroid patients with GD who had been under treatment and were still positive for anti-thyrotropin receptor antibodies (intractable GD), 20 euthyroid patients with GD in remission and 45 healthy controls. The frequency of the T allele and the TT genotype were higher in patients with severe HD than in those with in mild HD. In contrast, the frequency of the CC genotype was higher in patients with intractable GD than in patients with GD in remission. In conclusion, the +869T/C polymorphism in the TGF-,1 gene is associated with the severity and intractability of autoimmune thyroid disease. [source] A Mediterranean diet rich in virgin olive oil may reverse the effects of the -174G/C IL6 gene variant on 3-year body weight changeMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue S1 2010Cristina Razquin Abstract Only a few studies have analyzed the effects of the potential interaction between the -174G/C polymorphism of IL6 gene and the adherence to the Mediterranean diet (MD) on adiposity indexes. Our aim was to investigate the interplay between the -174G/C polymorphism of the IL6 gene and a Mediterranean-style diet on body weight changes after 3 years of nutritional intervention in a high cardiovascular risk population. A total of 737 participants, aged 55,80 years were assigned to a low-fat diet or to a Mediterranean-style diet group with high intake of virgin olive oil (VOO) or nuts. Anthropometric measurements were taken at baseline and after 3-year follow-up. The -174G/C polymorphism of the IL6 gene was genotyped. Minor allele frequency (C) was 0.39. At baseline, the CC genotype was associated with higher measures of adiposity. After 3 years, a significant interaction (p=0.028) was found between the polymorphism (GG+GC versus CC) and the nutritional intervention: CC subjects following the MD+VOO had the lowest body weight gain. In conclusion, at baseline, CC subjects for the -174G/C polymorphism of IL6 had the highest body weight and BMI. However, after 3 years of nutritional intervention with MD+VOO, these subjects were predicted to have the greatest reduction in body weight. [source] Interleukin 12B gene polymorphism and apparent resistance to hepatitis C virus infectionCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2008D. Hegazy Summary Cellular immunity with interferon gamma production could have a role in protection from hepatitis C virus (HCV). Interleukin (IL)-12 is a key cytokine in promoting such anti-viral T helper 1 (Th1) responses. We hypothesized that a genetic background able to promote cellular responses may be associated with apparent protection from infection and have investigated the distribution of the functional 1188A/C polymorphism of IL-12B in HCV exposed but uninfected cases. The frequency of the high IL-12-producing C allele was determined by restriction enzyme genotyping in 76 exposed,uninfected individuals and 105 healthy controls. Overall, the C allele was found in 27·6% of exposed,uninfected cases compared with 16·7% of healthy controls [,2 = 6·3, P = 0·02, odds ratio (OR) = 1·9, 95% confidence interval (CI) = 1·1,3·2]. CC genotype was found in 10·5% of exposed,uninfected cases compared with 0·9% controls (,2 = 9·3, P = 0·01, OR = 12, 95% CI = 1·5,100). Individuals at high risk of HCV infection yet who remain uninfected may be resistant in some way to infection. In our cohort of exposed,uninfected cases a genetic background of enhanced IL-12 production was associated with apparent resistance to HCV infection. This lends support to a central role for cellular immune responses in protecting from infection. [source] A novel promoter polymorphism in the gene encoding complement component 5 receptor 1 on chromosome 19q13.3 is not associated with asthma and atopy in three independent populationsCLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2004K. C. Barnes Summary Background The inflammatory functions of complement component 5 (C5) are mediated by its receptor, C5R1, which is expressed on bronchial, epithelial, vascular endothelial and smooth muscle cells. A susceptibility locus for murine allergen-induced airway hyper-responsiveness was identified in a region syntenic to human chromosome 19q13, where linkage to asthma has been demonstrated and where the gene encoding C5R1 is localized. Objective The aim of this study was to screen for novel polymorphisms in the C5R1 gene and to determine whether any identified polymorphisms are associated with asthma and/or atopy and whether they are functional. Methods Single-nucleotide polymorphism (SNP) detection in the gene encoding C5R1 was performed by direct sequencing. Genotyping was performed in three populations characterized for asthma and/or atopy: (1) 823 German children from The Multicenter Allergy Study; (2) 146 individuals from Tangier Island, Virginia, a Caucasian isolate; and (3) asthma case,parent trios selected from 134 families (N=783) in Barbados. Functional studies were performed to evaluate differences between the wild-type and the variant alleles. Results We identified a novel SNP in the promoter region of C5R1 at position ,245 (T/C). Frequency of the ,245C allele was similar in the German (31.5%) and Tangier Island (36.3%) populations, but higher in the Afro-Caribbean population (53.0%; P=0.0039 to <0.0001). We observed no significant associations between the ,245 polymorphism and asthma or atopy phenotypes. Upon examination of the functional consequences of the ,245T/C polymorphism, we did not observe any change in promoter activity. Conclusion This new marker may provide a valuable tool to assess the risk for C5a-associated disorders, but it does not appear to be associated with asthma and/or atopy. [source] Mannose-binding lectin gene polymorphisms in relation to periodontitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 11 2008Anna Louropoulou Abstract Aim: To investigate the correlation of six functional polymorphisms in the MBL gene with MBL plasma levels in relation to periodontitis. Material and Methods: A total of 92 periodontitis patients and 70 controls, all of Caucasian origin, were included. Patients and controls were genotyped for the L/H, X/Y, P/Q, A/D, A/B and A/C polymorphisms. Distributions of genotypes, rate of allele carriage and allele frequencies were compared between patients and controls. Patients and controls were subdivided in groups of genotypes. Plasma MBL levels were compared between different genotype groups. Results: On the basis of genotyping, three phenotypes with regard to mannose-binding lectin (MBL) production were distinguished: high-producers, low-producers and deficient subjects. No differences in the genotype frequencies were observed between patients and controls. Within patients and controls, subjects with the high-producing genotypes had significantly higher MBL plasma levels than low-producers and deficient subjects (p<0.001). Plasma MBL was higher in low-producer patients compared with low-producer controls (padjusted=0.021). Conclusion: No association could be observed between MBL gene polymorphisms and susceptibility to periodontitis in Caucasians. However, now that genotyping could distinguish the low producing and deficient subjects from the high-producers, it was observed, for the first time, that MBL acts as a weak acute-phase protein in periodontitis. [source] The association between MIF-173 G>C polymorphism and prostate cancer in southern ChineseJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2009G.X. Ding MD Abstract Background and Objectives Accumulating epidemiological and molecular evidence suggests that inflammation is an important component in the etiology of PCa. Macrophage migration inhibitory factor (MIF) plays an important role in the pro- and anti-inflammatory response to infection. This study is aimed at investigating the potential association between MIF-173 G>C polymorphism, Gleason score, clinical stage, and prostate-specific antigen (PSA) value with respect to PCa incidence among the Han nationality in Southern China. Methods Genotyping was performed by using tetraprimer polymerase chain reaction (PCR) on 259 PCa patients and 301 cancer-free controls. Results We found that the MIF-173*C variant allele was significantly associated with an increased risk of PCa [adjusted odd ratio (OR),=,2.99, 95% confident interval (CI): 1.94,4.60] and higher Gleason scores from the PCa subjects (adjusted OR,=,10.72, 95% CI: 5.35,21.49). In addition, we noted that the MIF ,173*C variant allele was related to higher clinical stages and PSA values in PCa patients (adjusted OR,=,15.68, 95% CI: 7.40,33.23; adjusted OR,=,4.37, 95% CI: 2.41,7.92, respectively). Conclusion Our data suggest that MIF-173 polymorphisms may be associated with a higher incidence of prostate cancer compared to controls, and appears to be associated with higher Gleason scores, higher clinical stages, and PSA values in those with prostate cancer. J. Surg. Oncol. 2009;100:106,110. © 2009 Wiley-Liss, Inc. [source] Genetic variability in CRTH2 polymorphism increases eotaxin-2 levels in patients with aspirin exacerbated respiratory diseaseALLERGY, Issue 3 2010N. S. Palikhe To cite this article: Palikhe NS, Kim S-H, Cho B-Y, Ye Y-M, Choi G-S, Park H-S. Genetic variability in CRTH2 polymorphism increases eotaxin-2 levels in patients with aspirin exacerbated respiratory disease. Allergy 2010; 65: 338,346. Abstract Introduction:, CRTH2 is expressed on the surface of eosinophils and has been shown to mediate PGD2-induced eosinophil migration in vitro. Eosinophilic infiltration in the upper and lower airways is the key feature of asthma. Considering the fact that eosinophil infiltration is prominent in the upper and lower airways of aspirin exacerbated respiratory disease (AERD) compared to aspirin-tolerant asthma (ATA) patients, we hypothesized that activation of eosinophils via dysregulation of the CRTH2 gene may play an important role and be an important marker for AERD. Methods:, The three study groups , 107 with AERD, 115 with ATA and 133 normal healthy controls (NC) , were recruited from Ajou University Hospital, South Korea. Two polymorphisms of the CRTH2 gene at -466T>C and -129C>A were genotyped using primer extension methods. Results:, AERD patients had significantly higher serum eotaxin-2 levels than did those with ATA (P = 0.034). A significant difference in the genotype frequencies of CRTH2 -466T>C was detected between AERD and ATA patients (P < 0.05). The serum eotaxin-2 level was significantly higher in AERD patients carrying the TT genotype of CRTH2 -466T>C than those with the CT and CC (P < 0.05). In vitro functional study demonstrated that the -466T allele had lower luciferase activity (P < 0.001) and lower mRNA expression with higher production of eotaxin-2 (P = 0.003) in human lung epithelial cells. EMSA showed that CRTH2 -466T produced a specific band with a higher affinity than CRTH2 -466C had. Conclusion:, The CRTH2 -466T>C polymorphism increases serum and cellular eotaxin-2 production through lowered CRTH2 expression, leading to eosinophilic infiltration in AERD patients. [source] Association of polymorphisms within the transforming growth factor-,1 gene with diabetic nephropathy and serum cholesterol and triglyceride concentrationsNEPHROLOGY, Issue 6 2010ADÁN VALLADARES-SALGADO ABSTRACT Aim: The TGF-, gene participates in the development of chronic kidney disease. We investigated whether the 869 T > C, 915 G > C and ,800 G > A polymorphisms of TGF-,1 are associated with diabetic nephropathy (DN). Methods: Polymorphisms were genotyped in 439 type 2 diabetes mellitus patients, 233 with diabetic nephropathy (DN+) and 206 without (DN,). The sample was characterized for relevant clinical and biochemical parameters. Results: The 869 T > C (P = 0.016; odds ratio (OR) = 1.818, 95% confidence interval (CI) = 1.128,2.930) and the 915 G > C polymorphisms (P = 0.008, OR = 4.073, 95% CI = 1.355,12.249) were associated with diabetic nephropathy. The 869 T > C variant was associated with total cholesterol levels: CC + CT genotypes had a mean cholesterol concentration of 5.62 ± 1.40 mmol/L vs a mean concentration of 5.15 ± 1.40 mmol/L for the TT genotype (P = 0.011). Triglycerides were also higher in CC + CT genotypes (2.49 ± 1.56 mmol/L) in comparison with TT homozygotes (2.1 ± 1.22 mmol/L, P = 0.042). Multivariate logistic regression showed that the polymorphisms 869 T > C and 915 G > C were independent predictors for DN (P = 0.049 and 0.046, respectively). Conclusion: The 869 T > C and 915 G > C polymorphisms within the TGF-,1 gene were associated with DN+. Lower cholesterol and triglycerides levels were observed in TT homozygotes for the 869 T > C polymorphism. The TGF-,1 869 T allele seems to confer protection against DN+. [source] ORIGINAL ARTICLE: Transforming Growth Factor-Beta1 Gene Polymorphisms in Korean Patients with Pre-eclampsiaAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Shin Young Kim Citation Kim SY, Lim JH, Park SY, Yang JH, Kim MY, Kim MH, Ryu HM. Transforming growth factor-beta1 (TGF-,1) gene polymorphisms in Korean patients with pre-eclampsia. Am J Reprod Immunol 2010; 63: 291,298 Problem, The aim of this study was to investigate whether c.869T>C (Leu10Pro) and c.915G>C (Arg25Pro) polymorphisms in exon1 of the transforming growth factor-beta1 (TGF-,1) gene are associated with development of pre-eclampsia (PE) in Korean women. Method of study, We analyzed blood samples from 164 patients with PE and 182 healthy pregnant women using the polymerase chain reaction and DNA sequencing. Results, The frequencies of the 869CC and combined TC/CC genotypes were higher in patients with PE than in healthy controls. In the PE with intrauterine growth restriction (IUGR), the frequencies of these genotypes were also higher than that in controls. Furthermore, the 869C allele frequency was significantly higher in both PE and IUGR-complicated PE than in controls. Multivariate analysis showed that the 869TC, CC, and combined TC/CC genotypes were associated with an increased risk of PE compared with the 869TT genotype. In addition, the 869TC, CC, and combined TC/CC genotypes were significantly associated with an increased risk of IUGR-complicated PE compared with the 869TT genotype. The TGF-,1 c.915G>C polymorphism was not detected in our population. Conclusion, Our findings indicate that the TGF-,1 c.869T>C polymorphism may be a genetic risk factor for PE and IUGR-complicated PE. [source] A functional polymorphism in Pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo,THE PROSTATE, Issue 5 2010Bin Xu Abstract BACKGROUND A G,>,C polymorphism (rs2910164) which is located in the sequence of miR-146a precursor, results in a change from a G:U pair to a C:U mismatch in its stem region. To explore whether rs2910164 plays any role in prostate cancer (CaP), we analyzed the association between miR-146a polymorphism and risk of CaP and the expression of miR-146a with different genotypes in CaP tissues in southern Chinese Han population. MATERIALS AND METHODS Two hundred fifty-one CaP and 280 control subjects were included in the cancer association study, and 15 CaP tissue samples were used to test the expression of the miRNA precursors by real-time quantitative reverse transcription PCR. RESULTS We found that subjects carrying CC homozygotes had a 0.65-fold reduced risk (95% CI,=,0.43,0.99) than those carrying GG/GC genotypes (P,=,0.03), and the C allele displayed a lower prevalence of CaP compared with the G allele (OR,=,0.73, 95% CI,=,0.57,0.94, P,=,0.01). Moreover, hsa-miR-146a quantification showed that homozygous carriers of the C-variant had significantly decreased miRNA levels compared to the carriers of the GG/GC genotype. CONCLUSIONS The natural genetic variation in pre-miR-146a affects the amount of mature miR-146a, contributes to the genetic predisposition to CaP. Prostate 70: 467,472, 2010. © 2009 Wiley-Liss, Inc. [source] Influence of Cyclooxygenase-2 (COX-2) Gene Promoter Polymorphism ,765 on Graft Loss After Renal TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2009C. Courivaud A G,C polymorphism has been identified in the human cyclooxygenase-2 (COX-2) gene promoter at position ,765 with C allele leading to a decreased promoter activity with low prostaglandin E2 (PGE2) production. PGE2 has strong immunomodulatory properties that could influence graft survival. We studied the association between this polymorphism and allograft failure in two independent cohorts of renal transplant recipients (RTRs) including a total of 603 patients. The functional effect of COX-2 gene promoter polymorphism was analyzed by measuring serum levels of PGE2. Median follow-up was 8.7 and 7.9 years for the first and second cohort, respectively. Analysis of 603 patients identified 20 CC (3.3%), 179 GC (29.7%) and 404 GG (67%) carriers. Patients with the GG genotype had significantly higher serum PGE2 concentrations than patients with the C allele. Carriers with a C allele have an independent increased risk of graft loss (hazard ratio (HR) 2.43 [95% CI 1.19,4.97], p = 0.015 for cohort 1; HR 1.72 [95% CI 0.99,3.77], p = 0.051 for cohort 2) compared to GG patients. COX-2 gene promoter polymorphism at position ,765 (G,C) is associated with a higher rate of graft loss in RTRs. Such findings may be used to influence immunosuppressive strategies and optimize patient management. [source] Association analysis between canine behavioural traits and genetic polymorphisms in the Shiba Inu breedANIMAL GENETICS, Issue 5 2009Y. Takeuchi Summary The relationships between behavioural trait data and the genotype of 15 polymorphisms in eight neurotransmitter-related genes were analysed in 77 dogs of the Shiba Inu breed, an indigenous Japanese dog. The data were obtained from a 26-item questionnaire on the dog's behaviour, distributed to the dog's owners, through veterinary hospitals and the Shiba Inu breed magazine. A factor analysis of the questionnaire items extracted eight factors accounting for 66.8% of the variance. An association analysis between these factors and genetic polymorphisms indicated that the polymorphism of c.471T>C in the solute carrier family 1 (neuronal/epithelial high-affinity glutamate transporter) member 2 (SLC1A2) gene was significantly associated with Factor 1, referred to as ,aggression to strangers'. This association remained stable in separate analyses of data from surveys obtained from the hospitals and those obtained from the magazine. The results suggest that the c.471T>C polymorphism is associated with some types of aggressive behaviour in the Shiba Inu. Further studies using other dog breeds are necessary to extend these findings to dogs in general. [source] Serotonin syndrome and the T102,C polymorphism of the 5-HT2A receptor: a case reportBIPOLAR DISORDERS, Issue 5 2008L Lattanzi No abstract is available for this article. [source] Genetic polymorphisms of cyclooxygenase-2 and colorectal adenoma risk: The Self Defense Forces Health StudyCANCER SCIENCE, Issue 3 2008Naoyuki Ueda Cyclooxygenase (COX) is a key enzyme in the formation of prostaglandins, and an inducible isoform of COX, COX-2, has been implicated in colorectal carcinogenesis. This study investigated the relation of COX-2 polymorphisms (,1195G>A, ,765G>C and 8160A>G) to colorectal adenomas in a case,control study of male officials in the Self Defense Forces (SDF). The study subjects were 455 cases of colorectal adenoma and 1052 controls with no polyps who underwent total colonoscopy. Genotypes were determined using the polymerase chain reaction,restriction fragment length polymorphism (PCR-RFLP) method with genomic DNA extracted from the buffy coat. Statistical adjustment was made for age, hospital, rank in the SDF, body mass index (BMI), cigarette smoking, and alcohol intake. A statistically non-significant decrease in the risk of colorectal adenomas was observed for the AA versus GG genotype of ,1195G>A polymorphism and for the GC versus GG genotype of ,765G>C polymorphism. None had the ,765CC genotype in either the case or control groups. No effect modification of overweight, smoking or alcohol use was observed for either ,1195G>A or ,765G>C polymorphism. The variant allele of the 8160A>G polymorphism was extremely rare. A haplotype of ,1195G, ,765G and 8160A alleles was associated with a modest increase in the risk (adjusted odds ratio [OR] 1.38, 95% confidence interval [CI] 0.99,1.91), and the increase was more evident for distal adenomas (adjusted OR 1.57, 95% CI 1.04,2.38). Another haplotype of ,1195A, ,765C and 8160A alleles showed an adjusted OR of 0.22 (95% CI 0.06,0.88). These findings add to evidence for the role of COX-2 in colorectal carcinogenesis and warrant further studies focusing on haplotypes. (Cancer Sci 2008; 99: 576,581) [source] A polymorphism in the apolipoprotein A5 gene is associated with weight loss after short-term dietCLINICAL GENETICS, Issue 2 2005J Aberle Apolipoprotein A5 is a recently discovered apolipoprotein involved primarily in triglyceride metabolism. Several single-nucleotide polymorphisms have been investigated since the initial report. The ,1131T > C polymorphism has been associated with higher triglyceride levels and a decreased high-density lipoprotein cholesterol as well as with susceptibility to coronary heart disease. However, no study has so far emphasized on the association of a dietary intervention with apolipoprotein A5 polymorphisms. In a group of 606 hyperlipaemic and overweight men, we investigated how a short-term fat restriction affects lipid traits and body mass index (BMI) in wildtype and carriers of the ,1131T > C polymorphism. Our result was that the reduction of BMI was significantly higher in C allele carriers (p = 0.0021). Since the ,1131T > C polymorphism predisposes to coronary heart disease, a restriction diet is an important therapeutic approach in ,1131T > C carriers. [source] Association of polymorphisms within the transforming growth factor-,1 gene with diabetic nephropathy and serum cholesterol and triglyceride concentrationsNEPHROLOGY, Issue 6 2010ADÁN VALLADARES-SALGADO ABSTRACT Aim: The TGF-, gene participates in the development of chronic kidney disease. We investigated whether the 869 T > C, 915 G > C and ,800 G > A polymorphisms of TGF-,1 are associated with diabetic nephropathy (DN). Methods: Polymorphisms were genotyped in 439 type 2 diabetes mellitus patients, 233 with diabetic nephropathy (DN+) and 206 without (DN,). The sample was characterized for relevant clinical and biochemical parameters. Results: The 869 T > C (P = 0.016; odds ratio (OR) = 1.818, 95% confidence interval (CI) = 1.128,2.930) and the 915 G > C polymorphisms (P = 0.008, OR = 4.073, 95% CI = 1.355,12.249) were associated with diabetic nephropathy. The 869 T > C variant was associated with total cholesterol levels: CC + CT genotypes had a mean cholesterol concentration of 5.62 ± 1.40 mmol/L vs a mean concentration of 5.15 ± 1.40 mmol/L for the TT genotype (P = 0.011). Triglycerides were also higher in CC + CT genotypes (2.49 ± 1.56 mmol/L) in comparison with TT homozygotes (2.1 ± 1.22 mmol/L, P = 0.042). Multivariate logistic regression showed that the polymorphisms 869 T > C and 915 G > C were independent predictors for DN (P = 0.049 and 0.046, respectively). Conclusion: The 869 T > C and 915 G > C polymorphisms within the TGF-,1 gene were associated with DN+. Lower cholesterol and triglycerides levels were observed in TT homozygotes for the 869 T > C polymorphism. The TGF-,1 869 T allele seems to confer protection against DN+. [source] Metabolic effects and the methylenetetrahydrofolate reductase (MTHFR) polymorphism associated with neural tube defects in southern Brazil,BIRTH DEFECTS RESEARCH, Issue 7 2004Têmis Maria Félix Abstract BACKGROUND The importance of metabolic factors in neural tube defects (NTDs) has been the focus of many investigations. Several authors have suggested that abnormalities in homocysteine metabolism, such as hyperhomocysteinemia, folate deficiency, and low vitamin B12, may be responsible for these malformations and that both nutritional factors and genetic abnormalities are associated with them. METHODS We conducted a case-control study to investigate the influence of biochemical and genetic factors in NTDs in infants in southern Brazil. Levels of folate, vitamin B12, total homocysteine (t-Hcy) and the 677C>T and 1298A>C polymorphisms of the MTHFR gene were analyzed in 41 NTD child,mother pairs and 44 normal child,mother control pairs. RESULTS Subjects in the case group had a higher mean blood folate level than those in the control group. The level of vitamin B12 was lower in mothers in the NTD group than in control mothers (p = 0.004). The level of t-Hcy was not different in the two groups, but t-Hcy and vitamin B12 were correlated (p = 0.002). There was no difference in the genotype distribution for 677C>T and 1298A>C polymorphisms of MTHFR in the case and control pairs. The level of t-Hcy was correlated with 677TT. CONCLUSIONS Despite the small sample in this study, we suggest that low vitamin B12 and, consequently, hyperhomocysteinemia are important risk factors for NTDs in our population. Birth Defects Research (Part A), 2004. © 2004 Wiley-Liss, Inc. [source] The influence of polymorphisms of VKORC1 and CYP2C9 on major gastrointestinal bleeding risk in anticoagulated patientsBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2008Ramón Montes Summary The VKORC1 c.,1639G>A and CYP2C9 c.430C>T and c.1075A>C polymorphisms have been associated with increased sensitivity to oral anticoagulants. However, their role in gastrointestinal bleeding is unknown. We studied the risk of gastrointestinal bleeding associated with these polymorphisms, and how this risk was influenced by the anticoagulant dose and the use of common drugs. Eighty-nine patients with gastrointestinal bleeding during acenocoumarol therapy and 177 patients free of bleeding during acenocoumarol therapy were studied. None of the three polymorphisms constituted a serious gastrointestinal bleeding risk factor. However, patients bearing at least one of these polymorphisms were at high risk, when they simultaneously met one of the following conditions: a weekly dose of acenocoumarol higher than 15 mg [adjusted Odds Ratio (OR) (95% confidence interval (CI) = 4·19 (1·59,11·04)]; amiodarone use [adjusted OR (95% CI) = 9·97 (1·75,56·89)]; or aspirin use [adjusted OR (95% CI) = 8·97 (1·66,48·34)]. The consumption of statins was associated with a lower risk of gastrointestinal bleeding [adjusted OR = 0·50 (0·26,0·99)]. The risk of gastrointestinal bleeding during acenocoumarol therapy in carriers of any of the studied polymorphisms is severely increased with exposure to weekly doses of acenocoumarol higher than 15 mg or the use of amiodarone or aspirin. [source] Endothelial nitric oxide synthase Glu298Asp, 4b/a, and ,786T>C gene polymorphisms and the risk of ischemic strokeACTA NEUROLOGICA SCANDINAVICA, Issue 2 2010S. Saidi Saidi S, Mallat SG, Almawi WY, Mahjoub T. Endothelial nitric oxide synthase Glu298Asp, 4b/a, and ,786T>C gene polymorphisms and the risk of ischemic stroke Acta Neurol Scand: 2010: 121: 114,119. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Background and purpose,,, Endothelial nitric oxide synthase (eNOS) gene polymorphisms were associated with reduced NO production, and were evaluated as risk factors for ischemic stroke (IS). We investigated the association between eNOS gene ,786T>C (promoter), 27-bp repeat 4b/4a (intron 4), and Glu298Asp (exon 7) polymorphisms with IS in 329 IS patients and 444 controls. Materials and methods,,, Glu298Asp and ,786T>C genotyping was done by PCR-RFLP, 4b/4a was assessed by PCR,ASA. The contribution of eNOS polymorphisms to IS was analyzed by haplotype and multivariate regression analysis. Results,,, Higher frequency of 298Asp allele was seen in IS patients (P = 1.2 × 10,10), which remained independently associated with IS on multivariate analysis after controlling for traditional cerebrovascular risk factors. Allele and genotype distribution of 4b/4a and ,786T>C polymorphisms were comparable between patient and controls. Significantly higher prevalence of 298Asp/4b/,786T and 298Asp/4b/,786C haplotypes were seen in IS cases, thus conferring a disease susceptibility nature to these haplotypes. Multivariate regression analysis confirmed the association of 298Asp/4b/,786T and 298Asp/4b/,786C haplotypes, and in addition identified 298Asp/4a/,786T haplotype to be independently associated with IS, after controlling for traditional cerebrovascular risk factors. Conclusions,,, Genetic variation at the eNOS locus represent genetic risk factor for increased susceptibility to IS. [source] Genetic variations in the leptin and leptin receptor genes are associated with type 2 diabetes mellitus and metabolic traits in the Korean female populationCLINICAL GENETICS, Issue 2 2008HR Han Type 2 diabetes mellitus (T2DM) is a metabolic disorder that is characterized by insulin resistance and hyperglycemia. Leptin inhibits the glucose-stimulated insulin secretion, and leptin receptors are present on , cells as well as on fat cells, thus enabling leptin to modulate both insulin secretion and action. Therefore, leptin (LEP) and leptin receptor (LEPR) genes could play a role in the regulation of glucose and insulin after an oral glucose load. For the association study of LEP and LEPR with T2DM and metabolic traits, 752 women from Seoul National University Hospital (SNUH data) and 532 women from the Korean Health and Genome Study (KHGS data) were selected. Using the SNUH data, we identified that LEP,632G>A and +4998A>C polymorphisms were marginally associated with T2DM, LEP+4950G>A was significantly associated with several metabolic traits, and LEPR+5193G>A, +7187A>C, +27265G>A, +35861T>C, and +52289A>G showed strongly significant association with body mass index (BMI). We observed reproducibility of these results using the KHGS data; LEP+4950G>A and +4998A>C were significantly associated with systolic blood pressure and low-density lipoprotein cholesterol level, respectively. In conclusion, we observed that several polymorphisms in LEPR that had previous reports of association with BMI were significantly replicated in our samples and newly found that some variations of LEP were associated with T2DM and metabolic traits. [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] Interleukin-6 Gene Polymorphism Is Related to Bone Mineral Density During and After Puberty in Healthy White Males: A Cross-Sectional and Longitudinal StudyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2000Mattias Lorentzon Abstract Bone mineral density (BMD) is under strong genetic control and is the major determinant of fracture risk. The cytokine interleukin-6 (IL-6) is an important regulator of bone metabolism and is involved in mediating the effects of androgens and estrogens on bone. Recently, a G/C polymorphism in position ,174 of the IL-6 gene promoter was found. We investigated this genetic polymorphism in relation to BMD during late puberty and to peak bone mass, in healthy white males. We identified the IL-6 genotypes (GG, GC, and CC) in 90 boys, age 16.9 ± 0.3 years (mean ± SD), using polymerase chain reaction (PCR). BMD (g/cm2) at the femoral neck, lumbar spine, and total body was measured using dual energy X-ray absorptiometry. The volumetric BMD (vBMD; mg/cm3) of the lumbar spine was estimated. Differences in BMD in relation to the genotypes were calculated using analysis of variance (ANOVA). Subjects with the CC genotype had 7.9% higher BMD of the femoral neck (p = 0.03), 7.0% higher BMD of the lumbar spine (p < 0.05), and 7.6% higher vBMD of the lumbar spine (p = 0.04), compared with their GG counterparts. Using multiple regression, the IL-6 genotypes were independently related to total body BMD (CC > GG; p = 0.03), humerus BMD (CC > GG; p < 0.05), neck BMD (CC > GG; p = 0.01), spine BMD (CC > GG; p = 0.01), and spine vBMD (CC > GG; p = 0.008). At age 19.3 ± 0.7 years (mean ± SD; 88 men) the IL-6 genotypes were still independent predictors for total body BMD (CC > GG; p = 0.03), humerus BMD (CC > GG; p = 0.03), spine BMD (CC > GG; p = 0.02), and spine vBMD (CC > GG; p = 0.003), while the IL-6 genotypes were not related to the increase in bone density seen after 2 years. We have shown that polymorphism of the IL-6 gene is an independent predictor of BMD during late puberty and of peak bone mass in healthy white men. [source] Urokinase gene 3,-UTR T/C polymorphism is associated with oral cancerJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 5 2004Ming-Hsui Tsai Abstract Urokinase is thought to be involved in the formation of oral cancer, although there is a lack of genetic evidence. Our aim was to study single nucleotide polymorphisms in order to investigate the possibility. A total of 130 oral cancer patients and 105 controls were studied. Polymerase chain reaction (PCR) based restriction analysis was used to identify the C/T polymorphism of the urokinase gene, which is located on the 3,-untranslated region (3,-UTR) of chromosome 10. There was a significant difference in the distribution of the urokinase gene 3,-UTR C/T polymorphism frequency between cancer patients and the normal control group (P<0.05). The "T" allele was prominent in the cancer group. The odds ratio for the risk of the "T" allele in cancer patients was 2.71 (95% CI=1.325,5.562). The cancer patients were further categorized according to gender and whether or not they were habitual smokers or betel nut chewers. These clinical parameters were then compared with tumor cell differentiation and tumor progression. No significant differences were found. Therefore, the urokinase gene 3,-UTR "T" allele is associated with oral cancer and may play a role in oral cancer formation. However, we did not find the relationship between tumor progression and this polymorphism. J. Clin. Lab. Anal. 18:276,279, 2004. © 2004 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||