Impact of MTHFR Gene Polymorphisms C677T and A1298C on Congenital Atrial Septal Defect Risk in an Iranian Cohort

Background: Congenital heart defects (CHD) are recognized as the most common heart abnormalities amongst newborns and children, and atrial septal defect (ASD) is recognized as one of the most frequent forms of CHD. Prior studies indicated that the methylenetetrahydrofolate reductase (MTHFR) gene contributes to the etiology of CHD. Therefore, we designed a case-control study to assess the possible role of the MTHFR gene, specifically the C677T (rs1801133) and A1298C (rs1801131) polymorphisms within the Iranian ASD population sample. Method: A total of 166 subjects (81 children diagnosed with ASD and 85 control participants) were enrolled in this research. Samples genotyped for MTHFR rs1801133 and rs1801131 polymorphisms using the PCR-RFLP and ARMS-PCR approaches. Results: Our results indicated that rs1801131 variant reduced the risk of ASD in codominant (OR [95%CI]: 0.41[0.21-0.83], P=0.012), dominant (OR[95%CI]: 0.48 [0.25-0.93], p=0.028) and increased the risk of ASD in codominant (OR[95%CI]: 2.68[1.39-5.16], P = 0.003), dominant (OR [95% CI]: 2.72 [1.43-5.14], P = 0.002), overdominant (OR [95% CI]: 2.50 [1.31-4.78], P = 0.005), and allelic (OR [95% CI]: 2.16 [1.27-3.69], P = 0.004) models. Conclusion: Our findings suggest that MTHFR rs1801133 and rs1801131 variants may potentially affect the onset of ASD.