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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The numerous effects of Helicobacter pylori have attracted significant attention. The most consistent and well appreciated effect is peptic ulcer. However, gastric cancer, growth retardation and coronary artery disease are among other sequelae of this chronic infection. This discussion describes a potential relationship among risk of coronary artery disease, the changes caused in gastric juice by H. pylori-induced gastritis, and the bioavailability of folates. Reduced folate absorption can occur in an environment of increased gastric juice pH and/or decreased ascorbic acid. This can, relatively rapidly, result in inadequate folate status which inhibits the methionine synthase reaction. Reduced methionine synthase activity increases the blood concentration of homocyst(e)ine which is known to be toxic to endothelial cells, and an independent risk factor for atherosclerosis. Decreased folate bioavailability may help explain the increased risk of coronary artery disease which has been observed in populations infected with H. pylori. It would also be consistent with the increased occurrence of this association in lower socioeconomic groups, and may also help explain the low incidence of gastric cancer in Africa, despite the high prevalence of H. pylori infection.
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PMID:Coronary artery disease associated with Helicobacter pylori infection is at least partially due to inadequate folate status. 935 95

Elevated plasma homocysteine is increasingly being recognized as a risk factor for coronary artery disease (CAD). Although there is general agreement on the importance of micronutrients and genetic predisposition to elevated plasma homocysteine, the exact influence of the known prevalent mutations in genes which regulate homocysteine metabolism is not clear. We studied 376 cases of individuals with premature CAD with respect to their fasting and post-methionine load (PML) total homocysteine (tHcy) concentrations. We also determined the presence or absence of the T833C and G919A mutations of the cystathionine-beta-synthase (CBS) gene, the C677T mutation of the methylene tetrahydrofolate reductase (MTHFR) gene, and the A2756G transition of the B12 dependent methionine synthase (MS) gene. Our objectives were therefore both to confirm the relationship of plasma homocysteine with premature CAD and to examine the importance of genetic influence on both fasting and PML homocysteine. Approximately 32% of the CAD patients had fasting hyperhomocysteinemia and 16% had PML hyperhomocysteinemia. Of these, 8.5% had both forms of hyperhomocysteinemia (combined hyperhomocysteinemia). The T133C mutation in the CBS gene and the thermolabile C677T mutation in the MTHFR gene seem to play an important role in the subset of individuals with combined hyperhomocysteinemia. The A2756G transition in the MS gene is not associated with elevated plasma tHcy. Many cases (47%) of hyperhomocysteinemia are not associated with micronutrient deficiencies, impaired renal function, and/or currently known genetic mutations. Further work is needed to study whether unknown mutations, particularly those residing in the intronic sequences of the genes involved in homocysteine metabolism, other environmental factors, or interaction of gene, nutrient, and environmental factors may be the cause of currently unexplained cases of mild hyperhomocysteinemia.
Atherosclerosis 1999 Mar
PMID:Genetic causes of mild hyperhomocysteinemia in patients with premature occlusive coronary artery diseases. 1020 91

Modest elevations of circulating homocysteine are common in patients with vascular disease. We explored interrelations between total plasma homocysteine levels and mutations in genes for three key enzymes in methionine-homocysteine metabolism. Methyltetrahydrofolate reductase (MTHFR) 677C-->T, cystathionine beta synthase (CBS) 68-bp insertion at exon 8, and methionine synthase (MS) 2756A-->G were typed in 685 Australian caucasian patients aged < or =65 years with and without angiographically documented coronary artery disease (CAD). We also assessed associations between homocysteine levels and extracellular superoxide dismutase (EC-SOD) and other CAD risk factors. There were significant correlations between plasma total homocysteine, and EC-SOD (r = 0.170, p = 0.001 for men; r = 0.241, p = 0.003 for women) and LDL (r = 0.153, p = 0.001 for men; r = 0.132, p = 0.081 for women). Levels were also significantly higher among patients with unstable angina (15.30+/-0.44 micromol/l for men, 14.44+/-0.74 micromol/l for women) than those without angina (13.98+/-0.38 micromol/l for men, 13.41+/-0.98 micromol/l for women) or with stable angina (14.00+/-0.37 micromol/l for men, 12.88+/-0.71 micromol/l for women). There were no significant associations between the levels and the presence or severity of CAD. The mutant MTHFR homozygotes tended to have higher levels and those with the MS and CBS mutations tended to have lower levels. We conclude that there is a significant correlation between plasma homocysteine levels and EC-SOD suggesting that elevated homocysteine may exert oxidative stress and that levels are associated with unstable angina, but not the occurrence or extent of coronary stenosis. The contributions to total plasma homocysteine levels of the common mutations of genes coding for the enzymes controlling homocysteine metabolism are modest.
Atherosclerosis 1999 Sep
PMID:Relationship between total plasma homocysteine, polymorphisms of homocysteine metabolism related enzymes, risk factors and coronary artery disease in the Australian hospital-based population. 1048 96

A moderately elevated plasma total homocysteine (tHcy), whether measured during fasting or post-methionine load (PML), is increasingly being recognized as a risk factor for coronary artery diseases (CAD). However, etiologies for moderately elevated plasma tHcy, particularly with regard to the role of genetic influence on plasma tHcy levels, are still not well understood. In the current investigation, we studied 1025 individuals with respect to the effect of the 68-bp insertion (844ins68 variant) of the cystathionine beta-synthase (CBS) gene, the A(2756)G transition of the B(12)-dependent methionine synthase (MS) gene and the C(677)T transition of the methylenetetrahydrofolate reductase (MTHFR) gene on fasting and 4 h PML tHcy. Of these individuals, 153 (14.9%) were heterozygous for the 68-bp insertion, 329 (32.1%) were heterozygous for the G(2756) allele and 122 (11.9%) were homozygous for the C(677)T transition. Individuals heterozygous for the insertion had significantly lower PML increase in tHcy concentrations, while individuals homozygous for the A(2756)G transition had significantly lower fasting tHcy levels. A 2-way ANOVA showed that there was no interaction between the 844ins68 and the A(2756)G transition for either fasting tHcy or PML increase in tHcy, confirming the fact that the effect of these two genotypes on plasma tHcy levels are additive. The effects are opposite but additive with the C(677)50% of all individuals in this study carried polymorphic traits, which predisposed them to either higher or lower plasma tHcy concentrations, thus providing new evidence of the importance of genetic influences as determinants of tHcy levels.
Atherosclerosis 2000 Mar
PMID:Polygenic influence on plasma homocysteine: association of two prevalent mutations, the 844ins68 of cystathionine beta-synthase and A(2756)G of methionine synthase, with lowered plasma homocysteine levels. 1070 24

Methionine synthase (MS) encodes an enzyme that catalyzes the remethylation of homocysteine to methionine using a methyl group donated by 5-methyltetrahydrofolate, which is the major circulating form of folate in the body. Functional genetic variants of the MS may alter total homocysteine (tHcy) as well as folate levels which are independent risk factors for vascular disease. The influence of a common genetic polymorphism (2756A-->G, D919G) of the MS gene on plasma tHcy and folate levels and its relation to the risk of myocardial infarction (MI) in a prospective study of male physicians in the US was investigated. A nested case-control study was conducted within the Physicians' Health Study which was originally designed as a double-blind trial of aspirin and beta-carotene among 22071 US male physicians, aged 40-84 years in 1982. Sixty-eight percent of participants also donated a blood sample. The study included 387 incident MI case and 767 controls matched on age, smoking status, and time from randomization in 6-month intervals. Individuals with GG genotype had a non-significant reduction of MI risk (RR 0.51, 95% CI 0.17-1.16) compared to individuals with DD genotype after adjusting for MI risk factors. The MS polymorphism was associated with decreased tHcy (10.55, 9.87 and 9.57 nmol/ml for DD, DG and GG genotypes, respectively) and increased folate levels (3.95, 3.78, 7.31 ng/ml for DD, DG and GG genotypes, respectively) only among controls but not cases. It was concluded that influence of the MS (D919G) polymorphism on the plasma tHcy and folate levels is at most moderate, but should be further investigated in other large prospective studies.
Atherosclerosis 2001 Feb 15
PMID:Influence of a methionine synthase (D919G) polymorphism on plasma homocysteine and folate levels and relation to risk of myocardial infarction. 1125 68

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

Asian Indians who have settled overseas and those in urban India have increased risk of coronary events. Reasons for this increased risk are thought to be genetic but are yet unclear. Advances in molecular cardiology have revealed a number of single nucleotide polymorphisms associated with atherosclerosis. In this review, gene polymorphisms that have been associated with coronary diseases among Indians are discussed. Topics include the genes involved in hyperlipidemia, hypertension, and homocysteine. Mutations in the low-density lipoprotein receptor (LDLR) gene resulting in familial hypercholesterolemia have strong association with premature atherosclerosis. Common polymorphism of the apolipoproteins (apo) B-100 and E genes have been associated with variation in lipid and lipoprotein levels. Recently identified polymorphisms in the apoC3 (T-455C, C-482T), and cholesteryl ester transfer protein (CETP) (B1/B2 allele) genes are associated with increased triglycerides and reduced high-density lipoprotein (HDL)-levels, a feature now also common among Asian Indians. Angiotensin-converting enzyme-deletion (DD) polymorphism has been shown to influence beta-blocker therapy in heart failure. Mutations in methylenetetrahydrofolate reductase (C667T), cystathionine beta-synthase (T833C), and methionine synthase (A2756G) genes cause hyperhomocysteinemia, an independent risk factor for atherothrombosis. As the genetics of atherosclerosis continues to evolve, these factors along with the newer emerging factors may become a part of the routine assessment, aiding prediction of future coronary events.
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PMID:Gene polymorphism and coronary risk factors in Indian population. 1247 35

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

Hyperhomocysteinemia, a risk factor for cardiovascular disease, can be caused by genetic mutations in enzymes of homocysteine metabolism. Homocysteine remethylation to methionine is catalyzed by folate-dependent methionine synthase, or by betaine-homocysteine methyltransferase (BHMT), which utilizes betaine as the methyl donor. Since genetic variants in folate-dependent remethylation have been reported to increase risk for cardiovascular disease and other common disorders, we screened BHMT for sequence changes that might alter risk for coronary artery disease (CAD). A variant in exon 6-R239Q-was identified. The frequency of this change was examined in 504 individuals who had undergone coronary angiography and were stratified into controls (those with no or mild disease) and cases (those with significant [>50% reduction in luminal diameter stenosis] 1-, 2-, 3-vessel disease). Although this variant did not affect plasma homocysteine, the QQ genotype was present in higher frequency in those with no or mild disease, compared with those with significant disease (11 vs. 6%), suggesting that it may decrease risk of CAD; a statistically-significant decrease was seen in the older subjects (13 vs. 7%). Multivariate analysis for the entire group revealed an odds ratio of 0.48 (95% CI: 0.21-1.06) for the QQ genotype; this association was similar in the younger (OR=0.36; 95% CI: 0.09-1.41) and older subjects (OR=0.42; 95% CI: 0.15-1.18). Our study suggests that the Q allele of the R239Q mutation may decrease the risk of CAD and that this variant warrants additional investigation of its relationship with the development of CAD as well as other homocysteine-dependent disorders.
Atherosclerosis 2003 Apr
PMID:Investigations of a common genetic variant in betaine-homocysteine methyltransferase (BHMT) in coronary artery disease. 1281 2

Homocysteine (Hcy) is a sulfur-containing amino acid produced when methionine is demethylated. The majority of Hcy undergoes transsulfuration to cysteine by cystathionine beta-synthase (CBS), of which vitamin B6 (pyridoxine) is an essential cofactor. The remainder of Hcy is remethylated by methionine synthase (MS), of which vitamin B12 (cobalamin) is an essential cofactor along with methylenetetrahydrofolate (MTHF). MTHF is generated by the enzyme MTHFR-reductase (MTHFR). High levels of Hcy can result from a variety of aquired factors (deficiency of vitamins B6, B12 and folic acid, high meat diet, smoking and others) or genetic (abnormalities of methionine--homocysteine metabolism). Hyperhomocysteinemia is associated with premature atherosclerosis and venous thromboembolism; so called "cholesterol of XXI. age". Results of many studies suggest that hyperhomocysteinemia, homozygous state for MTHFR gene mutation, folate deficiency are probably risk factors for recurrent fetal loss, intrauterine fetal death, thrombo-embolic disease in pregnancy, neural tube defects and congenital cardiac malformation at infants and other placental diseases (pre-eclampsia, placental abruption and intrauterine growth restriction IUGR). Those irregularities are very interesting and important for obstetricians and gynecologists. The plasma homocysteine values can be modulated by vitamins, vitamin B6 and folic acid in particular. The potential for research and possible prevention in this area is immense.
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PMID:[Hyperhomocysteinemia and pregnancy complications]. 1518 72


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