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Homocysteine Concentrations (homocysteine + concentration)

Distribution by Scientific Domains
Medical Sciences70%
Life Sciences25%

Kinds of Homocysteine Concentrations

  • plasma homocysteine concentration
    		•
  • total homocysteine concentration
    		•

    Selected Abstracts

    Homozygous thermolabile variant of the methylenetetrahy-drofolate reductase gene: a potential risk factor for hyperhomo-cysteinaemia, CVD, and stroke in childhood

    DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2001
    Mara Prengler
    In this study of 118 children (median age 5.1 years; range 6 months to 17 years) with ischaemic stroke or transient ischaemic attack (TIA), 22 children (19%) were homozygous for the thermolabile variant of the methylenetetrahydrofolate reductase allele (t-MTHFR), compared with nine of 78 (12%) of a reference population (p=0.18, OR 1.76, 95% CI 0.76 to 4.04). Of those with cerebrovascular disease (CVD), 17 of 84 were homozygous for the t-MTHFR allele (p=0.13 compared with the reference population (OR 1.95, 95% CI 0.81 to 4.65). There was a significant (p<0.025) increment of plasma total homocysteine concentration in homozygotes for the t-MTHFR allele compared with heterozygotes, negatives for the t-MTHFR allele, and control children with no history of stroke. In four of 12 homozygotes for the t-MTHFR allele, plasma homocysteine levels were raised, compared with three of 38 of those who were negative or heterozygous (p=0.047; OR 5.8, 95% CI 1.1 to 31.2). Homozygotes for the t-MTHFR allele were significantly more likely to have a recurrent event than those who were negative or heterozygous (Cox regression p=0.031, hazard ratio 2.18, 95% CI 1.08 to 4.42). These data suggest that homozygosity for the t-MTHFR allele is associated with raised homocysteine levels in children and is a risk factor for primary and secondary stroke and TIA. [source]

    Methylenetetrahydrofolate reductase gene C677T mutation is related to the defects in the internal elastic lamina of the artery wall

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2002
    P. 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]

    Low Plasma Vitamin B12 Is Associated With Lower BMD: The Framingham Osteoporosis Study

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2005
    Katherine L Tucker
    Abstract Vitamin B12 is important to DNA synthesis and may affect bone formation. We examined the association between this vitamin and BMD in 2576 adults. Men with plasma B12 < 148 pM had significantly lower BMD at the hip, and women at the spine, relative to those with higher B12, and trends were similar for both at all sites. Low vitamin B12 may be a risk factor for low BMD. Introduction: Vitamin B12 is important to DNA synthesis and may affect bone formation. It has been linked to osteoblastic activity in clinical studies and cell culture. Materials and Methods: We examined the relationship between plasma vitamin B12 status and BMD in 2576 adult participants in the Framingham Offspring Osteoporosis Study (1996,2001). BMD was measured by DXA at the hip and spine. Plasma vitamin B12 was measured by radioassay. Mean BMD measures were estimated for four categories of vitamin B12 concentration, based on commonly used cut-offs, using analysis of covariance, adjusted for age, BMI, physical activity score for the elderly (PASE), alcohol use, smoking status, total calcium and vitamin D intake, season of bone measurement, and for women, menopause status and current estrogen use. Further adjustment for protein intake and total homocysteine concentration was also performed. Results: Both men and women with vitamin B12 concentrations <148 pM had lower average BMD than those with vitamin B12 above this cut-off. These differences were significant (p < 0.05) for men at most hip sites and for women at the spine. Significance remained after further adjustment for protein intake and plasma homocysteine. Conclusions: Vitamin B12 deficiency may be an important modifiable risk factor for osteoporosis. [source]

    Effect of bezafibrate on plasma homocysteine concentration in men with lower extremity arterial disease

    JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2004
    P. K. MacCallum
    No abstract is available for this article. [source]

    Hyperhomocysteinemia in pediatric and young adult renal transplant recipients

    PEDIATRIC TRANSPLANTATION, Issue 2 2004
    Amir Belson
    Abstract:, Hyperhomocysteinemia (HHcy) has been recently identified as an important and reversible cardiovascular risk factor in adult and pediatric renal transplant recipients. A retrospective cross-sectional analysis of 70 pediatric and young adult renal transplant recipients was performed to determine the prevalence, and important clinical and laboratory correlates of HHcy. Total homocysteine concentration, free and protein bound, was determined by fluorescence polarization immunoassay using an IMX analyzer. Hyperhomocysteinemia was defined as a serum homocysteine (Hcy) level above the 95th percentile for age. Fifty-four of 70 patients (77%) had HHcy. Comparison of patients with HHcy with patients without HHcy demonstrated no statistical difference in age (p = 0.35), gender (p = 0.76) or donor type (p = 0.20). Patients with HHcy had significantly lower calculated creatinine clearance values (Ccr) (p = 0.02), 67.3 ± 21.2 mL/min/1.73 m2 vs. 90.7 ± 32.3 mL/min/1.73 m2 for patients without HHcy. Immunosuppression did not correlate with the diagnosis of HHcy. Stepwise logistic regression identified patient age (0.18, p = 0.013) and Ccr (,0.04, p = 0.011) as significant variables. In conclusion, HHcy is more common than expected in pediatric renal transplant recipients. Patients with Ccr <80 mL/min/1.73 m2 were statistically more likely to have a diagnosis of HHcy. We recommend that Hcy levels should be evaluated in this high risk population. [source]

    Rate and determinants of progression of atherosclerosis in systemic lupus erythematosus

    ARTHRITIS & RHEUMATISM, Issue 10 2007
    Mary J. Roman
    Objective To determine the rate of atherosclerosis progression as well as the relationship of traditional risk factors, systemic lupus erythematosus (SLE),related factors, and treatment to atherosis progression in SLE patients. Methods Outpatients in the Hospital for Special Surgery SLE Registry underwent serial carotid ultrasound and clinical assessment in a longitudinal study. Results Among 158 patients, 77 (49%) had persistent absence of atherosclerosis (carotid plaque), 36 (23%) had unchanged atherosclerosis, and 45 (28%) had progressive atherosclerosis, defined as a higher plaque score (new plaque in 25 patients and more extensive plaque in 20 patients) after a mean ± SD interval of 34 ± 9 months. Multivariate determinants of atherosclerosis progression were age at diagnosis (odds ratio [OR] 2.75, 95% confidence interval [95% CI] 1.67,4.54 per 10 years, P < 0.001), duration of SLE (OR 3.16, 95% CI 1.64,6.07 per 10 years, P < 0.001), and baseline homocysteine concentration (OR 1.24, 95% CI 1.06,1.44 per ,moles/liter, P = 0.006). SLE patients with stable plaque and progressive plaque differed only in baseline homocysteine concentration. Atherosclerosis progression was increased across tertiles of homocysteine concentration (16.2%, 36.4%, and 56.1%; P = 0.001), and homocysteine tertile was independently related to progression of atherosclerosis (OR 3.14, 95% CI 1.65,5.95 per tertile, P < 0.001). Less aggressive immunosuppressive therapy and lower average prednisone dose were associated with progression of atherosclerosis in univariate, but not multivariate, analyses. Inflammatory markers and lipids were not related to atherosclerosis progression. Conclusion Atherosclerosis develops or progresses in a substantial minority of SLE patients during short-term followup (10% per year on average). Older age at diagnosis, longer duration of SLE, and higher homocysteine concentration are independently related to progression of atherosclerosis. These findings show that aggressive control of SLE and lowering of homocysteine concentrations are potential means to retard the development and progression of atherosclerosis in SLE. [source]

    The Effect of Glutathione Modulation on the Concentration of Homocysteine in Plasma of Rats

    BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2000
    Kjell K. Øvrebø
    Elevated plasma homocysteine concentration in humans is associated with increased risk of arteriosclerosis and ischaemic heart disease. We studied whether the plasma homocysteine concentration could be changed by administration of drugs that modulate the concentration of glutathione in both plasma and tissue. Male wistar rats received reduced glutathione (0.5 mmol/kg), N -acetylcysteine (0.5 mmol/kg), L-buthionine-[S,R]-sulfoximine (2 mmol/kg) or Ringer acetate intravenously. Twenty min. later an arterial blood sample was drawn for the measurement of homocysteine and other thiols in the plasma. The thiols were quantified by reversed-phase ion-pair liquid chromatography and fluorescence detection. The total homocysteine concentration in plasma of fasted rats was 6.1±0.5 ,M. Intravenous administration of reduced glutathione or N -acetylcysteine reduced the homocysteine concentration in plasma significantly by 51% to 3.0±0.3 ,M and 63% to 2.2±0.2 ,M, respectively (P<0.05). In contrast, L-buthionine-[S,R]-sulfoximine increased the concentration of homocysteine by 41% to 8.6±0.6 ,M (P<0.05). The glutathione concentration in plasma was 19.5±1.9 ,M in controls and was unchanged by N -acetylcysteine administration. Reduced glutathione increased plasma glutathione to 379.7±22.9 ,M (P<0.05), whereas L-buthionine-[S R]-sulfoximine lowered the plasma glutathione concentration to 5.3±0.4 ,M. Homocysteine was negatively correlated to the glutathione (r=,0.399, P<0.01) and the cysteine (r=,0.52, P<0.01) concentrations in plasma. Our conclusion is that modulation of the glutathione levels influences the concentration of homocysteine in plasma of rats. [source]

    Quantification of intracellular homocysteine by stable isotope dilution liquid chromatography/tandem mass spectrometry

    BIOMEDICAL CHROMATOGRAPHY, Issue 1 2007
    Yuehua Huang
    Abstract A precise and accurate stable isotope dilution liquid chromatography/tandem mass spectrometry method for the analysis of intracellular homocysteine has been developed. An internal standard, [2H8]-homocystine, was added to cell pellets from EA.hy 926 cells grown in culture under low and high folate concentrations. d,l -dithiothreitol was used to reduce cellular homocystine to homocysteine. Cellular proteins were precipitated by the addition of formic acid in acetonitrile. After centrifugation, a portion of the supernatant was analyzed by liquid chromatography/tandem mass spectrometry. Using a Supelcosil cyano column with an Applied Biosystems API 4000 triple quadrupole mass spectrometer, the SRM transitions for homocysteine (m/z 136 to m/z 90) and [2H4]-homocysteine (m/z 140 to m/z 94) were monitored. The method was validated by conducting five replicate analyses on three different days at four different concentrations (concentrations at the lower limit of quantitation and expected lower quartile, mid-range and upper quartile). The limit of detection was 2 ng/106 EA.hy 926 cells. Using this method, the intracellular homocysteine concentration in EA.hy 926 cells ranged from 10 to 36 ng/106 cells. Copyright © 2006 John Wiley & Sons, Ltd. [source]

    Single nucleotide polymorphism in CTH associated with variation in plasma homocysteine concentration

    CLINICAL GENETICS, Issue 6 2004
    J Wang
    Plasma total homocysteine (tHcy) concentration, an independent risk factor of atherosclerosis, has numerous genetic and environmental determinants. While the thermolabile polymorphism in MTHFR encoding methylenetetrahydrofolate reductase is the best-studied genetic factor associated with variation in plasma tHCy, other candidate genes are being evaluated. Recently, we discovered that cystathioninuria was caused by mutations in the CTH gene encoding cystathionine ,-lyase, an enzyme that converts cystathionine to cysteine in the trans-sulfuration pathway. We also identified a common single nucleotide polymorphism (SNP), namely c.1364G>T (S403I) in exon 12 of CTH. In the current analysis, we studied the association of genotypes of this SNP with plasma tHcy concentrations in 496 Caucasian subjects. CTH 1364T/T homozygotes had significantly higher mean plasma tHcy concentration than subjects with other genotypes, and the effect sizes of CTH and MTHFR genotypes were similar. The findings suggest that common variation in CTH may be a determinant of plasma tHcy concentrations. [source]

    Reduced plasma total homocysteine concentrations in Type 1 diabetes mellitus is determined by increased renal clearance

    DIABETIC MEDICINE, Issue 3 2005
    B. A. J. Veldman
    Abstract Introduction Elevated plasma levels of total homocysteine are related to the development of vascular complications. Patients with diabetes mellitus are particularly at risk for the development of these complications. Several factors determine plasma total homocysteine including renal function. Aims As early Type 1 diabetes is characterized by a relative glomerular hyperfiltration, increased renal clearance could contribute to decreased levels of homocysteine as observed in Type 1 diabetes mellitus. Therefore we investigated the relationship between plasma total homocysteine and the glomerular filtration rate (GFR). Methods In 92 Type 1 diabetes patients and 44 control subjects, we measured GFR and effective renal plasma flow (ERPF) by means of continuous infusion of inulin and p-aminohippurate. Fasting plasma total homocysteine was measured using high performance liquid chromatography. Results GFR (121 ± 21 resp. 104 ± 14 ml/min; P < 0.001) and ERPF (563 ± 127 resp. 516 ± 121 ml/min; P = 0.05) were significantly higher in Type 1 diabetes patients as compared with control subjects. Plasma total homocysteine was reduced in Type 1 diabetes patients as compared with control subjects (11.0 ± 4.5 resp. 13.4 ± 7 µmol/l; P = 0.01). Plasma total homocysteine was strongly correlated with GFR (Type 1 diabetes patients: r = ,0.43, P < 0.001; control subjects: r = ,0.39, P = 0.01). Conclusion GFR is a major determinant of plasma total homocysteine levels in Type 1 diabetes patients as well as control subjects. The reduced plasma total homocysteine levels in diabetes patients can be explained by an increased GFR. [source]

    Epigenetic DNA Hypermethylation of the HERP Gene Promoter Induces Down-regulation of Its mRNA Expression in Patients With Alcohol Dependence

    ALCOHOLISM, Issue 4 2006
    Stefan Bleich
    Background: Elevated plasma homocysteine concentrations can influence genomic and gene-specific DNA methylation in peripheral blood cells. The aim of this study was to investigate in patients with alcohol dependence, who show chronically elevated homocysteine levels, whether DNA methylation pattern within the HERP (homocysteine-induced endoplasmic reticulum protein) promoter region and expression of HERP mRNA is altered. Methods: The HERP mRNA expression level was measured by quantitative PCR in the blood of 66 male alcoholic patients and 55 nondrinking healthy controls. Epigenetic genomic DNA methylation status and HERP promoter methylation were measured with a nonradioactive elongation assay. Results: We observed a significant increase (7.6%) in the HERP promoter DNA methylation in patients with alcohol dependence (t test, t=,2.45, p<0.02) when compared with healthy controls (80.4%, SD 14.5), which was significantly associated with their elevated homocysteine levels (multiple linear regression, p<0.007). Furthermore, we found a significantly lower HERP mRNA expression in patients with alcohol dependence (t test, ,7.61 ,CT; SD 1.87, p<0.001) when compared with healthy controls (,6.04 ,CT; SD 2.41). The lowered HERP mRNA expression in alcoholic patients was best explained by the hypermethylation of the regulatory HERP gene promoter (regression analysis, p=0.004). Conclusions: To our knowledge, this is the first study evaluating HERP mRNA expression and its specific gene promoter methylation in alcoholic patients. As hypermethylation of DNA is an important epigenetic factor in the down-regulation of gene expression, and as HERP has been considered to play an essential role within the intracellular defense system, these findings may be useful in the understanding and treatment of different disease conditions associated with alcohol dependence. [source]

    G1793A polymorphisms in the methyl- enetetrahydrofolate gene: Effect of folic acid on homocysteine levels

    MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 8 2006
    Sandra 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]

    Betaine and homocysteine concentrations in foods

    PEDIATRICS INTERNATIONAL, Issue 4 2002
    Akiko Sakamoto
    Abstract Background: Betaine (Bet) supplementation is an effective strategy for dietary treatment of homocystinuria. However,previous reports on diet therapy have only examined methionine (Met) and cystine concentrations, but not those of Bet and homocysteine(Hcy) in food items. We set up a hypothesis that there are some food items, which contain a small amount of Met, but a great amountof Hcy and Bet. Methods: We measured Bet and Hcy concentrations in 58 food items, which were regarded as containing low Met. Results: Products of wheat flour are rich in Bet. The amount of Bet in food items investigated in this study is muchsmaller than the dose used to treat homocystinuria patients. Vegetables contained little Hcy, however sprouted beans and sprouted alfalfaseeds contained ample Hcy. Conclusion: Patients with homocystinuria do not have to be too concerned about Hcy in food items because the amountis small. Therefore, we encourage homocystinuria patients to continue a low Met diet therapy without anxiety of Hcy and Bet, and if necessary,Bet will be supplemented. [source]

    Serum folate and homocysteine levels in patients with obsessive-compulsive disorder

    PSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 5 2005
    MURAD ATMACA md
    Abstract Previous studies have shown that folate deficiency, increased homocysteine, impaired metylation have been identified in depressive disorder. Recently, growing research has resulted in the biological association between obsessive-compulsive disorder (OCD) and affective disorders. Therefore, in the present study it was evaluated whether or not folate and homocysteine levels changed. Serum folate and homocysteine concentrations were measured in 23 patients with OCD and in same number of controls. In addition, all patients were assessed by Yale-Brown Obsession Compulsion Scale (Y-BOCS). Serum folate values were significantly lower in OCD patients than in controls, while homocysteine concentrations were higher in patients compared with controls. Serum folate values were significantly and negatively related to Y-BOCS scores. Total serum homocysteine concentrations were positively correlated to Y-BOCS scores and the duration of illness. There was a trend toward a negative correlation between the concentrations of serum folate and homocysteine. In conclusion, we identified that a group of patients with OCD might have folate deficiency, higher homocysteine levels and probable impaired metylation and monoamine metabolism. [source]

    The Reduced Folate Carrier (SLC19A1) c.80G>A Polymorphism is Associated with Red Cell Folate Concentrations Among Women

    ANNALS OF HUMAN GENETICS, Issue 5 2009
    Anna Stanis, awska-Sachadyn
    Summary Low folate status may be a consequence of suboptimal intake, transport or cellular utilization of folate and, together with elevated homocysteine, is a recognized risk factor or marker for several human pathologies. As folate transport across cell membranes is mediated in part by the reduced folate carrier (RFC1), variants within SLC19A1, the gene that encodes RFC1, may influence disease risk via an effect on folate and/or homocysteine levels. The present study was undertaken to assess the association between the SLC19A1 c.80G>A polymorphism and folate/homocysteine concentrations in healthy young adults from Northern Ireland. The SLC19A1 c.80G>A polymorphism was not strongly associated with either serum folate or homocysteine concentrations in either men or women. However, in women, but not in men, this polymorphism explained 5% of the variation in red blood cell (RBC) folate levels (P= 0.02). Relative to women with the SLC19A1 c.80GG genotype, women with the GA and AA genotypes had higher RBC folate concentrations. Consequently, compared to women with the SLC19A1 c.80GA and AA genotypes, women who are homozygous for the 80G allele may be at increased risk of having a child affected with a neural tube defect and of developing pathologies that have been associated with folate insufficiency, such as cardiovascular disease. [source]

    Rate and determinants of progression of atherosclerosis in systemic lupus erythematosus

    ARTHRITIS & RHEUMATISM, Issue 10 2007
    Mary J. Roman
    Objective To determine the rate of atherosclerosis progression as well as the relationship of traditional risk factors, systemic lupus erythematosus (SLE),related factors, and treatment to atherosis progression in SLE patients. Methods Outpatients in the Hospital for Special Surgery SLE Registry underwent serial carotid ultrasound and clinical assessment in a longitudinal study. Results Among 158 patients, 77 (49%) had persistent absence of atherosclerosis (carotid plaque), 36 (23%) had unchanged atherosclerosis, and 45 (28%) had progressive atherosclerosis, defined as a higher plaque score (new plaque in 25 patients and more extensive plaque in 20 patients) after a mean ± SD interval of 34 ± 9 months. Multivariate determinants of atherosclerosis progression were age at diagnosis (odds ratio [OR] 2.75, 95% confidence interval [95% CI] 1.67,4.54 per 10 years, P < 0.001), duration of SLE (OR 3.16, 95% CI 1.64,6.07 per 10 years, P < 0.001), and baseline homocysteine concentration (OR 1.24, 95% CI 1.06,1.44 per ,moles/liter, P = 0.006). SLE patients with stable plaque and progressive plaque differed only in baseline homocysteine concentration. Atherosclerosis progression was increased across tertiles of homocysteine concentration (16.2%, 36.4%, and 56.1%; P = 0.001), and homocysteine tertile was independently related to progression of atherosclerosis (OR 3.14, 95% CI 1.65,5.95 per tertile, P < 0.001). Less aggressive immunosuppressive therapy and lower average prednisone dose were associated with progression of atherosclerosis in univariate, but not multivariate, analyses. Inflammatory markers and lipids were not related to atherosclerosis progression. Conclusion Atherosclerosis develops or progresses in a substantial minority of SLE patients during short-term followup (10% per year on average). Older age at diagnosis, longer duration of SLE, and higher homocysteine concentration are independently related to progression of atherosclerosis. These findings show that aggressive control of SLE and lowering of homocysteine concentrations are potential means to retard the development and progression of atherosclerosis in SLE. [source]

    Homocysteine metabolism and its relation to health and disease

    BIOFACTORS, Issue 1 2010
    Kelly T. Williams
    Abstract Homocysteine is a metabolic intermediate in methyl group metabolism that is dependent on a number of nutritional B-vitamin cofactors. An emerging aspect of homocysteine metabolism is its relation to health and disease. Perturbations of homocysteine metabolism, particularly intracellular and subsequently circulating accumulation of homocysteine (i.e., hyperhomocysteinemia), are associated with vascular disease risk, as well as other pathologies. However, intervention with B-vitamin supplementation has been shown to successfully restore normal homocysteine concentrations, but without concomitant reductions in disease risk. Thus, the mechanistic relation between homocysteine balance and disease states, as well as the value of homocysteine management, remains an area of intense investigation. [source]

    Genetic and lifestyle variables associated with homocysteine concentrations and the distribution of folate derivatives in healthy premenopausal women

    BIRTH DEFECTS RESEARCH, Issue 8 2010
    Carolyn M. Summers
    Abstract BACKGROUND Low folate and high homocysteine (Hcy) concentrations are associated with pregnancy-related pathologies such as spina bifida. Polymorphisms in folate/Hcy metabolic enzymes may contribute to this potentially pathogenic biochemical phenotype. METHODS The study comprised 26 Caucasian and 23 African-American premenopausal women. Subjects gave fasting blood samples for biochemical phenotyping and genotyping. Total Hcy (tHcy) and both plasma and red blood cell (RBC) folate derivatives (i.e. tetrahydrofolate [THF], 5-methylTHF [5-MTHF], and 5,10-methenylTHF [5,10-MTHF]) were measured using stable isotope dilution liquid chromatography, multiple reaction monitoring, and mass spectrometry. Eleven polymorphisms from nine folate/Hcy pathway genes were genotyped. Tests of association between genetic, lifestyle, and biochemical variables were applied. RESULTS In African American women, tHcy concentrations were associated (p < 0.05) with total RBC folate, RBC 5-MTHF, B12, and polymorphisms in methionine synthase (MTR) and thymidylate synthase (TYMS). In Caucasian women, tHcy concentrations were not associated with total folate levels, but were associated (p < 0.05) with RBC THF, ratios of RBC 5-MTHF:THF, and polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR) and MTR. In African Americans, folate derivative levels were associated with smoking, B12, and polymorphisms in MTR, TYMS, methionine synthase reductase (MTRR), and reduced folate carrier1 (RFC1). In Caucasians, folate derivative levels were associated with vitamin use, B12, and polymorphisms in MTHFR, TYMS, and RFC1. CONCLUSIONS Polymorphisms in the folate/Hcy pathway are associated with tHcy and folate derivative levels. In African American and Caucasian women, different factors are associated with folate/Hcy phenotypes and may contribute to race-specific differences in the risks of a range of pregnancy-related pathologies. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc. [source]

    Evaluation of infant methylenetetrahydrofolate reductase genotype, maternal vitamin use, and risk of high versus low level spina bifida defects,

    BIRTH DEFECTS RESEARCH, Issue 3 2003
    Kelly A. Volcik
    BACKGROUND Several studies have suggested that homozygosity for the C677T 5,10-methylenetetrahydrofolate reductase (MTHFR) variant is a potential risk factor for neural tube defects (NTDs), as individuals homozygous for the C677T allele have slightly elevated homocysteine concentrations under conditions of low folic acid intake. It has been hypothesized that maternal folic acid supplementation prevents NTDs by partially correcting reduced MTHFR activity associated with the variant form of the enzyme. METHODS Genomic DNA was extracted from newborn screening blood spots obtained from 145 infants with spina bifida (SB) and 260 nonmalformed control infants. The MTHFR C677T genotype was determined by restriction enzyme digestion of PCR amplification products with Hinf1. We investigated whether infant MTHFR genotype influenced the risk for the anatomic level of the SB lesion (high vs. low); we also explored whether maternal vitamin use influenced this risk. RESULTS Compared to controls, the frequency of SB infants with the homozygous 677 TT genotype was greatest in those infants with high level SB defects (26%; odds ratio [OR] = 2.9; 95% confidence interval [CI] = 0.9,10.1) than for those with low level SB defects (22%; OR = 1.8; 95% CI = 0.9,3.2). Furthermore, homozygous 677TT infants whose mothers did not use vitamins containing folic acid had a modestly increased risk of SB (OR = 1.8; 95% CI = 0.8,3.9), with this risk increasing more than three-fold (OR = 5.5; 95% CI = 0.8,28.1) for those infants with high level SB defects whose mothers did not use vitamins. CONCLUSIONS Based upon our observations, it is suggested that the association between the infant MTHFR homozygous variant genotype and spina bifida risk may be conditional upon both lesion level and maternal vitamin use. Birth Defects Research (Part A) 67:154,157, 2003. © 2003 Wiley-Liss, Inc. [source]

    Serum homocysteine concentrations in children with growth hormone (GH) deficiency before and after 12 months GH replacement

    CLINICAL ENDOCRINOLOGY, Issue 5 2004
    Valentina Esposito
    Summary objective, This open, prospective study was designed to evaluate the effect of growth hormone deficiency (GHD) and GH replacement therapy on serum homocysteine (Hcy) concentration in children with GHD. subjects, Seventeen prepubertal children with GHD (11 boys and six girls) aged 8·6 ± 1·9 years were studied before and after 12 months of GH replacement therapy at a dose of GH of 30 µg/kg/day. Seventeen healthy children acted as controls and were matched for age, sex and body mass index (BMI). methods, At study entry, height, weight, blood pressure, serum Hcy, serum IGF-I, total-low density lipoprotein (LDL)- and high density lipoprotein (HDL) cholesterol, triglycerides, free T4, free T3, vitamin B12, folate, glucose and creatinine were measured in all subjects. The atherogenic index (AI) was also calculated as the ratio of total cholesterol/HDL cholesterol (T/HDL). In GHD children these parameters were also revaluated after 12 months of GH therapy. results, At study entry height and serum IGF-I were significantly lower, as expected, in GHD patients than in controls (P < 0·0001 and P < 0·007, respectively). Serum Hcy levels were significantly higher in GHD patients than in healthy children (8·4 ± 2·9 vs. 6·0 ± 2·9 µmol/l; P < 0·03), although the absolute values were within the normal values for age and sex. There were no significant differences at baseline with respect to blood pressure, serum vitamin B12, folate, fT3, fT4, lipid profile, creatinine and glucose levels. After 12 months of GH replacement therapy height and serum IGF-I increased significantly compared to pretreatment values (P < 0·0001); serum Hcy levels decreased significantly (6·0 ± 3·3 µmol/l; P < 0·002) compared to baseline values, becoming similar to control values. Total cholesterol (3·5 ± 0·6 mmol/l) and the AI (2·5 ± 0·8) decreased significantly with respect to both pretreatment (4·2 ± 1·0 mmol/l; P < 0·0002 and 3·4 ± 0·8; < 0·002, respectively) and control values (4·2 ± 0·4 mmol/l; P < 0·0005 and 3·3 ± 1·1; P = 0·02, respectively). conclusions GHD in children is associated with higher serum levels of Hcy compared to controls, without significantly affecting the lipid profile. GH replacement for 12 months significantly decreased the Hcy levels and improved the lipid profile with a decrease of total cholesterol and the total/HDL cholesterol ratio, compared to pretreatment values. Given the small number of patients, further larger studies are needed to clarify whether these results may have significant effects in the prevention of cardiovascular disease in adulthood. [source]

    Endothelial markers and homocysteine in patients with classic Fabry disease

    ACTA PAEDIATRICA, Issue 2002
    K Demuth
    Aim: Fabry disease is an X-linked inborn error of glycosphingolipid metabolism due to the deficient activity of ,-galactosidase A, a lysosomal enzyme. It is a multisystem disorder characterized by progressive renal insufficiency, with added morbidity from cardio- and cerebrovascular involvement. The recent availability of genetically engineered enzyme offers an effective targeted treatment approach, but also emphasizes the need for surrogate markers to delineate organ damage and monitor the efficacy of enzyme replacement therapy (ERT). Methods: Multiple endothelial factors and plasma homocysteine concentrations were investigated in 12 consecutive hemizygous males with classic Fabry disease and 15 controls as part of an exhaustive baseline evaluation prior to ERT. Results: Compared with the controls, plasma concentrations of homocysteine were significantly (p > 0.01) higher in patients with Fabry disease in the absence of chronic renal failure or vitamin deficiency. Plasma concentrations of vascular cell adhesion molecule-1 were also significantly (p > 0.05) higher in the patients, and there was a trend for decreased endothelin-1 levels. No difference was found in serum intercellular adhesion molecule-1, plasma P-selectin, serum E-selectin and plasma thrombomodulin between the patients and controls. Conclusions: The results do not reveal measurable evidence for endothelial and leukocyte activation that could reliably serve as surrogate markers for routine monitoring of the efficacy of ERT in patients with Fabry disease. While the exact origin and clinical significance of hyperhomocysteinaemia in Fabry disease remains to be studied in a larger cohort of patients carefully monitored for their concurrent medications, especially carbamazepine, we suggest that patients may benefit from folic acid or multivitamin therapy to treat this additional vascular risk factor, when present. [source]