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BMC Cardiovascular Disorders
Published in: BMC Cardiovascular Disorders 1/2021

01-12-2021 | Patent Ductus Arteriosus | Research

Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring

Authors: Mengting Sun, Tingting Wang, Peng Huang, Jingyi Diao, Senmao Zhang, Jinqi Li, Liu Luo, Yihuan Li, Letao Chen, Yiping Liu, Jianhui Wei, Xinli Song, Xiaoqi Sheng, Jiabi Qin

Published in: BMC Cardiovascular Disorders | Issue 1/2021

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Abstract

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.
Appendix
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Metadata
Title
Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring
Authors
Mengting Sun
Tingting Wang
Peng Huang
Jingyi Diao
Senmao Zhang
Jinqi Li
Liu Luo
Yihuan Li
Letao Chen
Yiping Liu
Jianhui Wei
Xinli Song
Xiaoqi Sheng
Jiabi Qin
Publication date
01-12-2021

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