Genetic and environmental influences on total plasma homocysteine and coronary artery disease (CAD) risk among South Indians

Background: Hyperhomocysteinemia, a documented risk factor for CAD is highly prevalent in Indians. The rationale behind the current study is to explore the genetic and environmental causes for such high prevalence as there are limited studies in this context. Methods: A total of 108 CAD cases and 108 controls were analyzed for tHcy and 4 folate pathway genetic polymorphisms [methylene tetra hydrofolate reductase (MTHFR) C677T, 5-methyltetrahydrofolate homocysteine methyl transferase (MTR) A2756G, methionine synthase reductase (MTRR) A66G and glutamate carboxypeptidase U (GCPII) C1561T] using reverse phase HPLC and PCR-RFLP methods respectively. Results: MTHFR 677T, MTRR 66A, GCPII 1561T, male gender, alcohol intake, smoking, diabetes, creatinine and hypertension were found to influence tHcy. After controlling for confounding factors, Hyperhomocysteinemia and two of its genetic determinants i.e. MTHFRC677T [OR: 1.96,95% CI: 1.06-3.61] and GCP II C1561T [OR: 2.09,95% CI: 1.09-3.97] were found to be associated with risk for CAD. Significant epistatic interactions were observed between MTHFR 677T/MTR 2756G and GCP II 1561T/MTRR 66G. Alcohol intake in subjects with MTR 2756G allele was found to inflate the risk for CAD [OR: 4.15, 95% CI: 1.35-12.69]. Conclusion: Hyperhomocysteinemia, C677T MTHFR and C1561T GCPII are risk factors for CAD. Potential gene gene and gene - environment interactions indicate the need for multi-variate analyses for risk prediction. (C) 2009 Elsevier B.V. All rights reserved.