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

Abstract

Background

Evidence suggests that periconceptional folic acid supplementation may prevent congenital heart disease (CHD). Methionine synthase reductase (MTRR) 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 MTRR gene with CHD risk in offspring.

Methods

A hospital-based case-control study involving 740 mothers of CHD cases and 683 health controls was conducted.

Results

The study showed that maternal MTRR gene polymorphisms at rs1532268 (C/T vs. C/C: aOR = 1.524; T/T vs. C/C: aOR = 3.178), rs1802059 (G/A vs. G/G: aOR = 1.410; A/A vs. G/G: aOR = 3.953), rs2287779 (G/A vs. G/G: aOR = 0.540), rs16879334 (C/G vs. C/C: aOR = 0.454), and rs2303080 (T/A vs. 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.

Conclusions

Maternal MTRR 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.

Keywords:

• Congenital heart disease
• folic acid
• homocysteine
• methionine synthase reductase
• polymorphisms

Acknowledgments

The authors thank all pediatricians and patients who participated in the study.

Ethical approval

The study received approval from the ethics committee of Xiangya School of Public Health Central South University (No: XYGW-2018-36) and was conducted based on the Helsinki declaration. The study protocol has been registered with the Chinese Clinical Trial Registry (No: ChiCTR1800018492). We obtained written informed consent from all mothers.

Author contributions

JBQ and TTW conceptualized and designed the study, coordinated all study phases. JHW and TTW analyzed the data and wrote the paper. XLS, YPL, JS, and MTS performed the experiments. JHW, JYD, JQL, YHL, LTC and SMZ collected and check the data. JHW, TTW, and JBQ controlled the quality of this study. All authors reviewed and approved the paper.

Disclosure statement

No potential conflict of interest was reported by the author(s). No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

Additional information

Funding

Funding for this study was provided by the National Natural Science Foundation Program of China [82073653 and 81803313], Hunan Outstanding Youth Fund Project [2022JJ10087], National Key Research and Development Project [2018YFE0114500], China Postdoctoral Science Foundation [2020M682644], Hunan Provincial Science and Technology Talent Support Project [2020TJ-N07], Hunan Provincial Key Research and Development Program [2018SK2063], Open Project from NHC Key Laboratory of Birth Defect for Research and Prevention [KF2020006], Natural Science Foundation of Hunan Province [2018JJ2551], Natural Science Foundation of Hunan Province of China [2022JJ40207], and Changsha Municipal Natural Science Foundation [kq2202470].