title: Association of polymorphism in the thermolabile 5, 10-methylene tetrahydrofolate reductase gene and hyperhomocysteinemia with coronary artery disease.
abstract: 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.
authors: Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors: Mohammad A
authors: MA
authors: Alam
authors: Syed A
authors: SA
authors: Husain
authors: Rajiv
authors: R
authors: Narang
authors: Shayam S
authors: SS
authors: Chauhan
authors: Madhulika
authors: M
authors: Kabra
authors: Suman
authors: S
authors: Vasisht
mesh_terms: D003324:Coronary Artery Disease / Q000150:complications* / Q000201:enzymology* / Q000235:genetics; D004795:Enzyme Stability; D020022:Genetic Predisposition to Disease; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000201:enzymology* / Q000235:genetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012044:Regression Analysis
chemical_list: D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)