母体 MTHFR 基因多态性与子女先天性心脏病发生的关联分析。
Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring.
机构信息
Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, 110 Xiangya Road, Changsha, 410078, Hunan, China.
NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, 78 Xiangchun Road, Changsha, 410008, Hunan, China.
出版信息
BMC Cardiovasc Disord. 2021 Jun 14;21(1):298. doi: 10.1186/s12872-021-02117-z.
BACKGROUND
Although many studies showed that the risk of congenital heart disease (CHD) was closely related to genetic factors, the exact pathogenesis is still unknown. Our study aimed to comprehensively assess the association of single nucleotide polymorphisms (SNPs) of maternal MTHFR gene with risk of CHD and its three subtypes in offspring.
METHODS
A case-control study involving 569 mothers of CHD cases and 652 health controls was conducted. Thirteen SNPs were detected and analyzed.
RESULTS
Our study showed that genetic polymorphisms of maternal MTHFR gene at rs4846052 and rs1801131 were significantly associated with risk of CHD in the homozygote comparisons (TT vs. CC at rs4846052: OR = 7.62 [95%CI 2.95-19.65]; GG vs. TT at rs1801131: OR = 5.18 [95%CI 2.77-9.71]). And six haplotypes of G-C (involving rs4846048 and rs2274976), A-C (involving rs1801133 and rs4846052), G-T (involving rs1801133 and rs4846052), G-T-G (involving rs2066470, rs3737964 and rs535107), A-C-G (involving rs2066470, rs3737964 and rs535107) and G-C-G (involving rs2066470, rs3737964 and rs535107) were identified to be significantly associated with risk of CHD. Additionally, we observed that a two-locus model involving rs2066470 and rs1801131 as well as a three-locus model involving rs227497, rs1801133 and rs1801131 were significantly associated with risk of CHD in the gene-gene interaction analyses. For three subtypes including atrial septal defect, ventricular septal defect and patent ductus arteriosus, similar results were observed.
CONCLUSIONS
Our study indicated genetic polymorphisms of maternal MTHFR gene were significantly associated with risk of fetal CHD in the Chinese population. Additionally, there were significantly interactions among different SNPs on risk of CHD. However, how these SNPs affect the development of fetal heart remains unknown, and more studies in different ethnic populations and with a larger sample are required to confirm these findings.
背景
虽然许多研究表明先天性心脏病（CHD）的风险与遗传因素密切相关，但确切的发病机制仍不清楚。我们的研究旨在综合评估母体 MTHFR 基因的单核苷酸多态性（SNP）与后代 CHD 及其三种亚型风险的关联。
方法
进行了一项病例对照研究，纳入了 569 例 CHD 患儿的母亲和 652 名健康对照者。检测并分析了 13 个 SNP。
结果
我们的研究表明，母体 MTHFR 基因的遗传多态性在 rs4846052 和 rs1801131 处的纯合子比较与 CHD 风险显著相关（TT 与 CC 相比，rs4846052：OR=7.62[95%CI 2.95-19.65]；GG 与 TT 相比，rs1801131：OR=5.18[95%CI 2.77-9.71]）。涉及 rs4846048 和 rs2274976 的 G-C、涉及 rs1801133 和 rs4846052 的 A-C、涉及 rs1801133 和 rs4846052 的 G-T、涉及 rs2066470、rs3737964 和 rs535107 的 G-T-G、涉及 rs2066470、rs3737964 和 rs535107 的 A-C-G 和涉及 rs2066470、rs3737964 和 rs535107 的 G-C-G 这六个单倍型也被确定与 CHD 风险显著相关。此外，我们观察到 rs2066470 和 rs1801131 作为两个基因座的模型以及 rs227497、rs1801133 和 rs1801131 作为三个基因座的模型在基因-基因相互作用分析中与 CHD 风险显著相关。对于包括房间隔缺损、室间隔缺损和动脉导管未闭在内的三种亚型，也观察到了类似的结果。
结论
本研究表明，母体 MTHFR 基因的遗传多态性与中国人群胎儿 CHD 的风险显著相关。此外，不同 SNP 之间存在显著的相互作用，与 CHD 的风险相关。然而，这些 SNP 如何影响胎儿心脏的发育仍不清楚，需要在不同种族人群中进行更大样本量的研究来证实这些发现。
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