Association of maternal methionine synthase reductase gene polymorphisms with the risk of congenital heart disease in offspring: a hospital-based case-control study

Evidence suggests that periconceptional folic acid supplementation may prevent congenital heart disease (CHD). Methionine synthase reductase (<i>MTRR</i>) is one of the key regulatory enzymes in the folate metabolic pathway. This study aimed to comprehensively evaluate the association of single nucleotide polymorphisms (SNPs) in the maternal <i>MTRR</i> gene with CHD risk in offspring. A hospital-based case-control study involving 740 mothers of CHD cases and 683 health controls was conducted. The study showed that maternal <i>MTRR</i> gene polymorphisms at rs1532268 (C/T <i>vs.</i> C/C: aOR = 1.524; T/T <i>vs.</i> C/C: aOR = 3.178), rs1802059 (G/A <i>vs.</i> G/G: aOR = 1.410; A/A <i>vs.</i> G/G: aOR = 3.953), rs2287779 (G/A <i>vs.</i> G/G: aOR = 0.540), rs16879334 (C/G <i>vs.</i> C/C: aOR = 0.454), and rs2303080 (T/A <i>vs.</i> T/T: aOR = 0.546) were associated with the risk of CHD. And seven haplotypes were observed to be associated with the risk of CHD, T-G-A haplotype (OR = 1.298), C-A-C-C (OR = 4.824) and A-G haplotype (OR = 1.751) were associated with increased risk of CHD in offspring; A-A-A (OR = 0.773), T-A-A (OR = 0.557), G-A-C-C (OR = 0.598) and G-C (OR = 0.740) were associated with decreased risk of CHD in offspring. Maternal <i>MTRR</i> gene polymorphisms were associated with CHD in offspring, and its haplotypes have affected the occurrence of CHD. Furthermore, given the complexity and heterogeneity of CHD, the mechanisms by which these factors influence offspring cardiac development remain unknown, and studies in larger samples in an ethnically diverse population are needed.