Rs4841587 in GATA4 and rs6999593 in DNMT1 gene associated with congenital heart diseases in the southeast of Iran

Abstract

BackgroundDifferent genetic and epigenetic variations are implicated in congenital heart diseases (CHDs). GATA4 and DNMT1 genes play an important role in embryonic heart development. We aim to investigate the correlation between rs4841587 in GATA4 and rs6999593 in DNMT1 genes with susceptibility and severity of symptoms in ventricular septal defects (VSDs) and tetralogy of fallot (TF) diseases in the southeast of Iran. MaterialsThis case-control study was evaluated 200 children diagnosed with VSDs or TF as well as 200 healthy controls. SNPs genotyping were performed using T-ARMS-PCR. Odds ratio (OR) and 95% confidence interval (CI), as well as Chi-square, was used to assess the strength of the association. ResultsTT genotype at rs4841587 in GATA4 was associated with the susceptibility of CHDs (OR = 2.02, 95% CI = 1.06–3.83, P = .031). Rs4841587 was related with VSDs under the dominant model (GT + TT vs. GG: OR = 1.70, 95% CI = 1.08–2.65, P = .020). However, no significant differences were observed in genotype frequencies between TF cases and controls at this position. AG genotype at rs6999593 in DNMT1 was strongly correlated with the risk of CHDs (OR = 2.27, 95% CI = 1.43–3.60, P = .000). Significant differences also were found between AG genotype with VSDs (OR = 2.12, 95% CI = 1.19–3.77, P = .011) and TF (OR = 2.58, 95% CI = 1.19–5.57, P = .016). Conclusionsrs4841587 and rs6999593 can be proposed as a significant marker for CHDs. Rs4841587 T/G polymorphism correlated with the susceptibility and severity of symptoms in VSDs. Moreover, rs6999593 A/G affects the susceptibility of VSDs and TF, in the southeast of Iran. However, further investigations are necessary to confirm these results.