Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidemiological evidence has revealed that an elevated plasma homocysteine level (hyperhomocysteinemia) confers an increased risk of cardiovascular disease and neural tube defects. Hyperhomocysteinemia is caused by both nutritional (e.g. folate, vitamins B(6) and B(12)) and genetic factors, including functional polymorphisms of key enzymes involved in homocysteine metabolism. One such enzyme, methionine synthase reductase (MTRR), maintains adequate levels of methylcob(III)alamin, the activated cofactor for methionine synthase, which catalyzes the remethylation of homocysteine to methionine. A common MTRR polymorphism, i.e. a 66 A-->G substitution specifying an isoleucine to methionine substitution (I22M), was recently identified. To assess the influence of this polymorphism on total plasma homocysteine (tHcy), we undertook a genotype/phenotype analysis in a study population of 601 Northern-Irish men, aged 30--49, for which biochemical and genetic data relevant to folate/homocysteine metabolism had already been acquired. The 66AA genotype has a frequency of 29% in this population. We established that there was a significant influence of MTRR genotype on tHcy ranking (P=0.004) and that the 66AA genotype contributes to a moderate increase in tHcy levels across the distribution [OR 1.59 (95% CI: 1.10--2.25) for the 66AA genotype to be in the upper half of the tHcy distribution, P=0.03]. The homocysteine-elevating effect of the 66AA genotype is independent of serum folate, vitamin B(12) and vitamin B(6) levels. Based on published estimates of the enhanced cardiovascular disease risk conferred by defined increments of plasma tHcy, we estimate that 66AA homozygotes have, on average, an approximately 4% increase in cardiovascular disease risk compared to 66GG homozygotes. This study provides the first evidence that the MTRR A66G polymorphism significantly influences the circulating tHcy concentration.
Atherosclerosis 2001 Aug
PMID:The methionine synthase reductase (MTRR) A66G polymorphism is a novel genetic determinant of plasma homocysteine concentrations. 1147 46

The metabolism of homocysteine requires contributions of several enzymes and vitamin cofactors. Earlier studies identified a common polymorphism of methylenetetrahydrofolate reductase that was associated with mild hyperhomocysteinemia. Common variants of two other enzymes involved in homocysteine metabolism, methionine synthase and methionine synthase reductase, have also been identified. Methionine synthase catalyzes the remethylation of homocysteine to form methionine and methionine synthase reductase is required for the reductive activation of the cobalamin-dependent methionine synthase. The methionine synthase gene (MTR) mutation is an A to G substitution, 2756A-->G, which converts an aspartate to a glycine codon. The methionine synthase reductase gene (MTRR) mutation is an A to G substitution, 66A-->G, that converts an isoleucine to a methionine residue. To determine if these polymorphisms were associated with mild hyperhomocysteinemia, we investigated subjects from two of the NHLBI Family Heart Study field centers, Framingham and Utah. Total plasma homocysteine concentrations were determined after an overnight fast and after a 4-h methionine load test. MTR and MTRR genotype data were available for 677 and 562 subjects, respectively. The geometric mean fasting homocysteine was unrelated to the MTR or MTRR genotype categories (AA, AG, GG). After a methionine load, a weak positive association was observed between change in homocysteine after a methionine load and the number of mutant MTR alleles (P-trend=0.04), but this association was not statistically significant according to the overall F-statistic (P=0.12). There was no significant interaction between MTR and MTRR genotype or between these genotypes and any of the vitamins with respect to homocysteine concentrations. This study provides no evidence that these common MTR and MTRR mutations are associated with alterations in plasma homocysteine.
Atherosclerosis 2003 Jan
PMID:Effects of polymorphisms of methionine synthase and methionine synthase reductase on total plasma homocysteine in the NHLBI Family Heart Study. 1248 50

We analyzed the association between the methylenetetrahydrofolate reductase (MTHFR) 677C>T and methionine synthase reductase (MTRR) 66A>G polymorphisms with serum homocysteine and with coronary artery disease (CAD) in 504 patients undergoing clinically-indicated angiography between July 1998 and January 1999. Significant CAD (>/=50% stenosis in >/=one artery, blinded to risk factors) was present in 271 patients (54%). Median homocysteine (micromol/l) was 8.8 (interquartile range: 7.5-10.7). The prevalence of the MTHFR TT, CT, and CC genotypes was 11, 44 and 45%, respectively. Median tHcy (with interquartile ranges) for the entire population was 8.8 (7.5-10.7), and for the TT, CT, and CC genotypes was 9.7 (8.2-11.4), 8.8 (7.5-10.7), and 8.6 (7.3-10.6) micromol/l, respectively (P=0.04). On multiple logistic regression analysis, the MTHFR TT genotype was associated with hyperhomocysteinemia (adjusted OR=3.57; 95% CI, 1.47-8.70), but not with significant CAD. The prevalence of the MTRR AA, AG, GG genotypes was 19, 50 and 31%, respectively. There were no differences in mean homocysteine, prevalence of hyperhomocysteinemia and significant CAD between the three genotypes. On multivariate analysis, the MTRR genotypes were not associated with serum homocysteine or with significant CAD.
Atherosclerosis 2003 Jun
PMID:Methylenetetrahydrofolate reductase (MTHFR) 677C>T and methionine synthase reductase (MTRR) 66A>G polymorphisms: association with serum homocysteine and angiographic coronary artery disease in the era of flour products fortified with folic acid. 1280 15

The association of variants of the gene encoding methionine synthase reductase (MTRR) with hyperhomocysteinemia, folate and Vitamin B(12) status in kidney graft recipients is unknown. We examined two mutations in MTRR in a cross-sectional study of 733 kidney graft recipients. The allele frequency of MTRR 66G was 0.55. 369 patients (50.3%) were heterozygous and 219 patients (29.9%) were homozygous for the mutation. None of the patients showed the 997C > G mutation. The allelic variants of MTRR 66A > G showed no significant association with total homocysteine (tHcy) levels, both in univariate analyses, and in a multivariate model controlling for age, gender, body mass index, renal function, time since transplantation, underlying kidney disease, as well as the MTHFR 677C > T/1298A > C genotypes. Similarly, no significant associations between the MTRR 66A > Ggenotypes and plasma folate or Vitamin B(12) levels were found. In conclusion, MTRR 66A > G has no major effect on tHcy, folate, or Vitamin B(12) plasma concentrations in kidney graft recipients.
Atherosclerosis 2004 May
PMID:Methionine synthase reductase MTRR 66A > G has no effect on total homocysteine, folate, and Vitamin B12 concentrations in renal transplant patients. 1513 49

Under study were features of allele polymorphism of genes of methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A 2756G), methionine synthase reductase (MTRR A66G) and methylenetetrahydrofolate dehydrogenase (MTHFD G1958A) in patients with atherosclerosis of the lower extremity arteries (ALEA). Patients with hyperhomocysteinemia (HHcy) had statistically significant increase of allele MTHFR 677T and MTRR 66GG as compared both with the control group and with the group of patients without HHcy. It suggests that polymorphism of genes involved in homocystein and folate metabolism might affect the risk of HHcy in patients with ALEA.
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PMID:[Features of allele polymorphism of genes involved in homocysteine and folate metabolism in patients with atherosclerosis of the lower extremity arteries]. 2020 90