Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, 110 Xiangya Road, Changsha, 410078, Hunan, China.
Department of Cardiothoracic Surgery, Hunan Children's Hospital, Changsha, Hunan, China.
BMC Pregnancy Childbirth. 2022 Jan 31;22(1):88. doi: 10.1186/s12884-022-04419-2.
MTHFD1 gene may affect the embryonic development by elevated homocysteine levels, DNA synthesis and DNA methylation, but limited number of genetic variants of MTHFD1 gene was focused on the association with congenital heart disease (CHD). This study examined the role of MTHFD1 gene and maternal smoking on infant CHD risk, and investigated their interaction effects in Chinese populations.
A case-control study of 464 mothers of CHD infants and 504 mothers of health controls was performed. The exposures of interest were maternal tobacco exposure, single nucleotide polymorphisms (SNPs) of maternal MTHFD1 gene. The logistic regression model was used for accessing the strength of association.
Mothers exposed to secondhand smoke during 3 months before pregnancy (adjusted odds ratio [aOR] = 1.56; 95% confidence interval [CI]: 1.13-2.15) and in the first trimester of pregnancy (aOR = 2.24; 95%CI: 1.57-3.20) were observed an increased risk of CHD. Our study also found that polymorphisms of maternal MTHFD1 gene at rs1950902 (AA vs. GG: aOR = 1.73, 95% CI: 1.01-2.97), rs2236222 (GG vs. AA: aOR = 2.38, 95% CI: 1.38-4.12), rs1256142 (GA vs.GG: aOR = 1.57, 95% CI: 1.01-2.45) and rs11849530 (GG vs. AA: aOR = 1.68, 95% CI: 1.02-2.77) were significantly associated with higher risk of CHD. However, we did not observe a significant association between maternal MTHFD1 rs2236225 and offspring CHD risk. Furthermore, we found the different degrees of interaction effects between polymorphisms of the MTHFD1 gene including rs1950902, rs2236222, rs1256142, rs11849530 and rs2236225, and maternal tobacco exposure.
Maternal polymorphisms of MTHFD1 gene, maternal tobacco exposure and their interactions are significantly associated with the risk of CHD in offspring in Han Chinese populations. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings.
Registration number: ChiCTR1800016635 .
MTHFD1 基因可能通过升高同型半胱氨酸水平、DNA 合成和 DNA 甲基化来影响胚胎发育，但该基因的少数遗传变异被集中用于研究其与先天性心脏病（CHD）的关联。本研究旨在探讨 MTHFD1 基因和母亲吸烟对婴儿 CHD 风险的作用，并在中国人中研究它们的交互作用。
对 464 名 CHD 患儿的母亲和 504 名健康对照母亲进行病例对照研究。感兴趣的暴露因素包括母亲的烟草暴露和母亲 MTHFD1 基因的单核苷酸多态性（SNP）。采用 logistic 回归模型评估关联的强度。
母亲在怀孕前 3 个月（调整后的优势比[aOR] = 1.56；95%置信区间[CI]：1.13-2.15）和怀孕早期（aOR = 2.24；95%CI：1.57-3.20）暴露于二手烟，CHD 发病风险增加。我们的研究还发现，母亲 MTHFD1 基因的 rs1950902（AA 与 GG：aOR = 1.73，95%CI：1.01-2.97）、rs2236222（GG 与 AA：aOR = 2.38，95%CI：1.38-4.12）、rs1256142（GA 与 GG：aOR = 1.57，95%CI：1.01-2.45）和 rs11849530（GG 与 AA：aOR = 1.68，95%CI：1.02-2.77）的多态性与 CHD 风险增加显著相关。然而，我们没有观察到母亲 MTHFD1 rs2236225 与后代 CHD 风险之间存在显著关联。此外，我们发现 MTHFD1 基因包括 rs1950902、rs2236222、rs1256142、rs11849530 和 rs2236225 的多态性与母亲烟草暴露之间存在不同程度的交互作用。
母亲 MTHFD1 基因多态性、母亲烟草暴露及其相互作用与汉族人群后代 CHD 风险显著相关。然而，需要在不同种族人群中进行更多具有更大样本量和前瞻性设计的研究来证实我们的发现。
注册号：ChiCTR1800016635。
