Association of a MiR-499 SNP and risk of congenital heart disease in a Chinese population

MicroRNAs (miRNAs) play an important role in heart development. Single nucleotide polymorphisms (SNPs) in miRNAs have been shown to associate with congenital heart disease (CHD). Methionine synthase (MTR), a key enzyme of folate metabolism, is involved in the early embryonic development. In this study, we aimed to test whether MTR is a direct target of miR-499, and to estimate the associations between miR-499 polymorphisms and the risk of CHD in Chinese population. Gene polymorphisms were analyzed in 1615 subjects including 792 healthy controls and 823 CHD patients. The miR-499 SNP were genotyped and the associations between the SNP frequencies and CHD were assessed by computing odds ratios (ORs) and 95% confidence intervals (95% CIs), as well as by applying Chi-square tests. Dual reporter assay was carried out to test whether MTR is a direct target gene of miR-499. The miR-499 rs374644 AG genotype was not associated with the CHD risk (AG vs. AA. OR=1.27, 95% CI=0.85-1.81, p=0.20). The GG genotype was associated with a significantly increased CHD risk (GG vs. AA. OR=5.33, 95% CI=1.80-15.83, p=0.001). The AG/GG variants were associated with a significantly increased CHD risk, compared with the AA genotype (OR=1.56, 95% CI=1.16-2.10, p=0.003). MiR-499 mimics inhibits the expression of MTR. MiR-499 directly targeted on MTR. Thus, our study suggested that miR-499 directly targets on MTR and the polymorphisms of rs3746444 may be associated with CHD risk in Chinese individuals.