Association between methylenetetrahydrofolatereductase gene (MTHFR) polymorphisms and homocysteine level in Thai patients with coronary artery disease

Methylenetetrahydrofolatereductase (MTHFR) is a key regulatory enzyme in folate and homocysteine (Hcy) metabolisms. Mutation of MTHFR gene leads to the increased levels of Hcy. Elevated blood Hcy level may induce oxidative injury to vascular endothelial cells and impairs vascular function leading to atherosclerosis. The aim of the present study was to investigate the relationships between MTHFR polymorphisms and total homocysteine (tHcy) level in Thai patients with coronary artery disease (CAD). A case-control study was performed in 352 subjects who were clinically suspected of having CAD and were undergoing coronary angiography at Queen Sirikit Heart Center of the Northeast, KhonKaen University. Based on angiographic results, 206 patients were categorized as CAD and 146 subjects were control. The polymorphisms of MTHFR C677T and A1298C were genotyped in subjects with CAD and control groups, using PCR-RFLP and AS-PCR techniques, respectively. Serum tHcy was determined using DiazymeHomocysteine Enzymatic Assay Kit (Diazyme, USA). The results demonstrated that the genotype and allele frequencies of MTHFR C677T and A1298C polymorphisms were not significantly different between control and CAD groups. Significant elevation of the relative frequency (%) of T carriers ( CT, TT) of C677T polymorphism was observed in all subjects and in male alone with higher level of tHcy as compared with lower level, either by using tHcy cut-off point at 15 μmol/L or by categorizing the tHcy concentration into 3 levels as £10, >10-15 and > 15μmol/L; a lower percentage of T carrier was always revealed in all subjects with lower level of tHcy. There was, however, no significant difference when observed in female subjects. In addition, the mean serum tHcy levels in the T carriers ( CT, TT ) of C677T were higher in all subjects as well as in male subjects alone (p<0.001) as compared with the CC genotype; there was apparently no difference observed in female subjects. There were no significant association between the A1298C polymorphism and serum tHcy, either by cut-off level or by mean level, as observed in all subjects as well as separated male and female groups. This study indicated that polymorphism of MTHFR C677T contributes to the risk of CAD by the effect on increase of blood tHcy concentration.