Association of genetic and epigenetic modification in MTHFR gene with coronary artery disease patients in North Indian population

Background: Methylene tetra hydro folate reductase (MTHFR) gene polymorphism C677T (rs180113) and DNA methylation in promoter region of MTHFR gene may contribute to the development of coronary artery disease however the results have been inconsistent across studies with different populations, so the aim of our study is to explore the association of polymorphism in MTHFR gene and methylation in promoter region with coronary artery disease (CAD) and other risk factor (lipid profile, homocysteine, vitamin B12 and folic acid levels) leading to CAD in of north Indian population. Methods: Total 100 CAD patients and 100 healthy controls were enrolled in the study. Genotyping of rs1801133 SNP (C677T) is done by PCR-RFLP and DNA methylation study in promoter region by methylation specific PCR. Lipid profile analysis by automated chemistry analyzers, serum homocysteine, folic acid and vitamin B12 was assayed by ELISA. Results: As per our finding the T allele (OR=3.03, 95% CI=1.74-5.27) and hyper methylation in promoter region of MTHFR increases the odds of coronary artery disease, (OR=3.05, 95% CI=1.7-5.6). Study participants with CT and TT genotype had significantly higher homocysteine (Hcy) (p=0.001), lower folic acid level (p=0.0), and HDL levels (p<0.0001) than those with CC genotype. The study subjects with hyper methylated promoter region have a significantly high homocystenemia levels (p=0.001). Conclusions: The TT genotype of the MTHFR C677T gene polymorphism and hyper methylation in promoter region of MTHFR, is associated with CAD and can be useful in identification of new biomarkers, development of preventive and therapeutic strategies for CAD.