Impact of A1298C Polymorphism of Methylenetetrahydrofolate Reductase Gene on Risk of Congenital Heart Disorders in Iranian Population

Congenital heart disorders (CHDs) encompass inborn defects of the heart compartments. Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene have continuously been reported as a modulating factor for CHDs. In a case-control study, the association of A1298C polymorphism of MTHFR gene with ventricular septal defect (VSD) and Tetralogy of Fallot (TOF), two common forms of CHDs, in the children of southeastern Iran was investigated. The presence of A1298C polymorphism was investigated using tetra-ARMS-PCR method, and statistical processes were carried out applying SPSS software (V:19). Males in the control group formed 40% and 60% (including 46.74% in VSD and 13.26% in in TOF). Although the association between gender and CHDs was not statistically significant, males had a higher risk of VSD (OR=1.7, 95% CI; 0.9-3.1, P=0.08). Overall frequency of AA, AC ,and CC genotypes of A1298C polymorphism were 55%, 43%, and 2% in CHDs patients respectively; while respective ratios were 50%, 48% and 2% in the controls (P 0.05). Patients with VSD were more commonly identified with AC+CC genotypes (52.8%) compared to TOF cases (23%, P=0.01). In stratified regression analysis, heterozygote genotype showed a significant protection against TOF (OR=0.3, 95% CI; 0.1-0.8, P=0.01). Frequency of variant allele was obtained 31.58% in CHD patients and 33.8% in the controls (P 0.05). Moreover, frequency of variant (C) allele was 35.2% in VSD compared to 18.8% in TOF (P 0.05). A1298C polymorphism of MTHFR gene seems to exert a significant protective effect against TOF.