PMID- 18074111 OWN - NLM STAT- MEDLINE DCOM- 20080620 LR - 20211020 IS - 0300-8177 (Print) IS - 0300-8177 (Linking) VI - 310 IP - 1-2 DP - 2008 Mar TI - Association of polymorphism in the thermolabile 5, 10-methylene tetrahydrofolate reductase gene and hyperhomocysteinemia with coronary artery disease. PG - 111-7 AB - OBJECTIVE: To determine the incidence of methylene tetrahydrofolate reductase (MTHFR) gene 677C-->T polymorphism and plasma homocysteine (Hcy) levels in a group of subjects who underwent coronary angiography, in an attempt to establish a correlation between these parameters and the severity of coronary artery disease (CAD) and to investigate the correlation between hyperhomocysteinemia (HHcy) and the presence of 677C-->T polymorphism. BACKGROUND: Elevated plasma Hcy level is an independent risk factor for CAD. A common mutation (677C-->T) in the gene coding for MTHFR has been reported to reduce the enzymatic activity and is associated with elevated levels of Hcy, especially in subjects with low folate intake. METHODS: The study group comprised of 84 patients with CAD and 100 age-and-sex matched controls who had no history or clinical evidence of CAD and/or MI. DNA was extracted from peripheral blood and genotypes were determined by polymerase chain reaction, restriction mapping with Hinf1, and gel electrophoresis. Conventional risk factors for CAD were prospectively documented. RESULTS: Allele and genotype frequencies in cases and control subjects were compatible with Hardy-Weinberg equilibrium. The frequencies of TT, CT, and CC genotypes among CAD patients were 4.8, 27.4, and 67.8% and in controls were 1.0, 19.0, and 80%. Hcy levels were higher in patients with triple-vessel disease compared to single and double vessel disease (P = 0.002). Multivariate analyses identified HHcy, diabetes mellitus, and hypertension as the independent predictors of CAD. CONCLUSIONS: HHcy appears to have a graded effect on the risk of CAD as well as the severity and extent of coronary atherosclerosis. Our findings support that homozygous genotype of MTHFR is a genetic risk factor for CAD. A further study with larger sample size including assessment of vitamin status is needed to better clarify the relationship between MTHFR genotypes and CAD. FAU - Alam, Mohammad A AU - Alam MA AD - Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India. FAU - Husain, Syed A AU - Husain SA FAU - Narang, Rajiv AU - Narang R FAU - Chauhan, Shayam S AU - Chauhan SS FAU - Kabra, Madhulika AU - Kabra M FAU - Vasisht, Suman AU - Vasisht S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071212 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0LVT1QZ0BA (Homocysteine) RN - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2)) SB - IM MH - Coronary Artery Disease/*complications/*enzymology/genetics MH - Enzyme Stability MH - *Genetic Predisposition to Disease MH - Homocysteine/metabolism MH - Humans MH - Hyperhomocysteinemia/*complications/*enzymology/genetics MH - Methylenetetrahydrofolate Reductase (NADPH2)/*genetics MH - Middle Aged MH - Multivariate Analysis MH - Phenotype MH - Polymorphism, Single Nucleotide/*genetics MH - Regression Analysis EDAT- 2007/12/13 09:00 MHDA- 2008/06/21 09:00 CRDT- 2007/12/13 09:00 PHST- 2007/05/29 00:00 [received] PHST- 2007/11/22 00:00 [accepted] PHST- 2007/12/13 09:00 [pubmed] PHST- 2008/06/21 09:00 [medline] PHST- 2007/12/13 09:00 [entrez] AID - 10.1007/s11010-007-9671-7 [doi] PST - ppublish SO - Mol Cell Biochem. 2008 Mar;310(1-2):111-7. doi: 10.1007/s11010-007-9671-7. Epub 2007 Dec 12.