Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410078.
Department of Cardiothoracic Surgery, Hunan Children's Hospital, Changsha 410007, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2022 Jan 28;47(1):52-62. doi: 10.11817/j.issn.1672-7347.2022.200992.
Maternal periconceptional folic acid supplement is by far the most effective primary prevention strategy to reduce the incidence of congenital heart disease (CHD) in offspring. It was revealed that the underlying mechanisms are complex, including a combination of genetic and environmental factors. The purpose of this study is to investigate the association between periconceptional folic acid supplement, the genetic polymorphisms of maternal folic acid receptor 1 gene () and folic acid receptor 2 gene () and the impact of their interaction on the risk of CHD in offspring, and to provide epidemiological evidence for individualized folic acid dosing in hygienic counseling.
A case-control study on 569 mothers of CHD infants and 652 mothers of health controls was performed. The interesting points were periconceptional folate supplements, single nucleotide polymorphisms (SNPs) of maternal gene and gene.
Mothers who took folate in the periconceptional period were observed a decreased risk of CHD [adjusted odds ratio (aOR)=0.58, 95% CI 0.35 to 0.95]. Our study also found that polymorphisms of maternal gene at rs2071010 (G/A vs G/G: aOR=0.67, 95% CI 0.47 to 0.96) and gene at rs514933 (T/C vs T/T: aOR=0.60, 95% CI 0.43 to 0.84; C/C vs T/T: aOR=0.55, 95% CI 0.33 to 0.90; the dominant model: T/C+ C/C vs T/T: aOR=0.59, 95% CI 0.43 to 0.81; and the addictive model: C/C vs T/C vs T/T: aOR=0.70, 95% CI 0.56 to 0.88) were significantly associated with lower risk of CHD [all <0.05, false discovery rate value (FDR_)<0.1]. Besides, significant interaction between periconceptional folate supplements and rs2071010 G→A (aOR=0.59, 95% CI 0.41-0.86) and rs514933 T→C (aOR=0.52, 95% CI 0.37 to 0.74) on CHD risk were observed (all <0.05, FDR_<0.1).
Periconceptional folate supplements, polymorphisms of gene and gene and their interactions are significantly associated with risk of CHD. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings.
母亲围孕期补充叶酸是迄今为止降低后代先天性心脏病（CHD）发生率最有效的一级预防策略。研究表明，其潜在机制复杂，包括遗传和环境因素的综合作用。本研究旨在探讨围孕期叶酸补充、母体叶酸受体 1 基因（）和叶酸受体 2 基因（）的遗传多态性及其相互作用对后代 CHD 风险的影响，为卫生咨询中的个体化叶酸剂量提供流行病学证据。
对 569 名 CHD 患儿母亲和 652 名健康对照母亲进行病例对照研究。感兴趣的点是围孕期叶酸补充、母亲基因和基因的单核苷酸多态性（SNP）。
围孕期服用叶酸的母亲 CHD 风险降低[调整后的优势比（aOR）=0.58，95%置信区间 0.35 至 0.95]。我们的研究还发现，母体基因 rs2071010（G/A 与 G/G：aOR=0.67，95%置信区间 0.47 至 0.96）和基因 rs514933（T/C 与 T/T：aOR=0.60，95%置信区间 0.43 至 0.84；C/C 与 T/T：aOR=0.55，95%置信区间 0.33 至 0.90；显性模型：T/C+C/C 与 T/T：aOR=0.59，95%置信区间 0.43 至 0.81；和相加模型：C/C 与 T/C 与 T/T：aOR=0.70，95%置信区间 0.56 至 0.88）与 CHD 风险显著降低相关[均<0.05，错误发现率（FDR_）值<0.1]。此外，还观察到围孕期叶酸补充与 rs2071010 G→A（aOR=0.59，95%置信区间 0.41 至 0.86）和 rs514933 T→C（aOR=0.52，95%置信区间 0.37 至 0.74）之间存在显著的交互作用（均<0.05，FDR_<0.1）。
围孕期叶酸补充、基因和基因多态性及其相互作用与 CHD 风险显著相关。然而，需要更多不同种族人群的更大样本量和前瞻性设计的研究来证实我们的发现。
