Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410078, China.
National Health Committee Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha 410028, China.
Nutrients. 2023 Aug 9;15(16):3502. doi: 10.3390/nu15163502.
Existing evidence supported that congenital heart defect (CHD) was associated with a combination of environmental and genetic factors. Based on this, this study aimed at assessing the association of maternal folic acid supplementation (FAS), genetic variations in offspring methylenetetrahydrofolate dehydrogenase (MTHFD)1 and MTHFD2 genes, and their interactions with CHD and its subtypes. A hospital-based case-control study, including 620 cases with CHD and 620 healthy children, was conducted. This study showed that the absence of FAS was significantly associated with an increased risk of total CHD and its subtypes, such as atrial septal defect (ASD). FAS during the first and second trimesters was associated with a significantly higher risk of CHD in offspring compared to FAS during the three months prior to conception. The polymorphisms of offspring MTHFD1 and MTHFD2 genes at rs2236222, rs11849530, and rs828858 were significantly associated with the risk of CHD. Additionally, a significantly positive interaction between maternal FAS and genetic variation at rs828858 was observed for the risk of CHD. These findings suggested that pregnant women should carefully consider the timing of FAS, and individuals with higher genetic risk may benefit from targeted folic acid supplementation as a preventive measure against CHD.
现有证据表明，先天性心脏病（CHD）是环境和遗传因素共同作用的结果。基于这一点，本研究旨在评估母体叶酸补充（FAS）、子女亚甲基四氢叶酸脱氢酶（MTHFD）1 和 MTHFD2 基因遗传变异，及其与 CHD 及其亚型的相关性。进行了一项基于医院的病例对照研究，包括 620 例 CHD 患儿和 620 例健康儿童。本研究表明，FAS 缺失与总 CHD 及其亚型（如房间隔缺损（ASD））的风险增加显著相关。与受孕前三个月相比，第一和第二孕期的 FAS 与子女 CHD 的风险显著增加相关。子女 MTHFD1 和 MTHFD2 基因 rs2236222、rs11849530 和 rs828858 多态性与 CHD 风险显著相关。此外，还观察到母体 FAS 与 rs828858 遗传变异之间存在显著的正交互作用，与 CHD 风险相关。这些发现表明，孕妇应仔细考虑 FAS 的时机，而遗传风险较高的个体可能受益于靶向叶酸补充作为预防 CHD 的措施。
