Association of maternal MTR gene polymorphism with offspring congenital heart disease: a case-control study

Abstract

ObjectiveTo explore the association between maternal methionine synthase (MTR) gene polymorphism and the risk of congenital heart disease (CHD) in offsprings. MethodsA case-control study was conducted among 464 biological mothers of CHD children and 504 biological mothers of healthy children in the Department of Cardiothoracic Surgery, Hunan Children's Hospital from November 2017 to December 2019. Single nucleotide polymorphisms (SNPs) of MTR gene was detected with MassArray time-of-flight mass spectrometry. The association between MTR SNPs and offspring CHD was analyzed with SPSS 24.0 software, and Haploview software was used in haplotype analysis. ResultsThe results of multivariate logistic regression analysis demonstrated that the SNPs of following MTR gene loci were significantly associated with increased risk of CHD incidence: rs1266164 (TT vs. CC: adjusted odds ratio [aOR] = 3.39, 95% confidence interval [95% CI]: 1.48 – 7.76; recessive model: aOR = 3.27, 95% CI: 1.44 – 7.45) and rs6668344 (dominant model: aOR = 1.55, 95% CI: 1.12 – 2.16); the results also revealed that SNPs of three MTR gene loci correlated with decreased risk of offspring CHD incidence included rs3768139 (CC vs. GG: aOR = 0.26, 95% CI: 0.11 – 0.58; dominant model: aOR = 0.29, 95% CI: 0.13 – 0.65; recessive model: aOR = 0.62, 95% CI: 0.45 – 0.85), rs1050993 (recessive model: aOR = 0.59, 95% CI: 0.42 – 0.82), and rs3820571 (GG vs. CC: aOR = 0.28, 95% CI: 0.12 – 0.64; recessive model: aOR = 0.56, 95% CI: 0.40 – 0.79). The haplotype TT and CT of rs6668344-rs3754255, AGTA of rs1805087-rs2275565-rs1266164- rs4659743, as well as AT and GT of rs1050993-rs6676866 were associated with the incidence risk of offspring CHD. ConclusionBoth the polymorphism and haplotype of maternal MTR gene might be associated with the incidence risk of offspring CHD.

Keywords

• congenital heart disease
• methionine synthase
• haplotype