Study on Maternal SNPs of MTHFR Gene and HCY Level Related to Congenital Heart Diseases

Hui Shi,Peng Huang,Rongbin Yu,Lijuan Wang,Ning Lin,Xiaoru Sun,Zhixin Jiang,Shiwei Yang,Mei Chen

doi:10.1007/s00246-020-02449-1

Abstract

The aim of this study is to evaluate the relationship between maternal single nucleotide polymorphisms (SNPs) of methylenetetrahydrofolate reductase (MTHFR) gene with plasma homocysteine (HCY) level and offspring congenital heart diseases (CHDs). 338 mothers with offspring CHDs as case group and 306 mothers of normal children as control group were recruited. Their pregnant histories were interviewed by questionnaire and the MTHFR rsl801133 and rsl801131 were genotyped. The case–control analysis was used to find out the relationship between maternal SNPs of MTHFR gene and offspring CHDs. And the plasma HCY concentration of the mothers of CHDs children was detected. This case–case study was intended to find out the relevance between maternal HCY level and SNPs of MTHFR gene. There were significant differences in the gender of children, occupation of mothers, family history with CHDs, history of abortion, history of adverse pregnancy, early pregnancy health, fetus during pregnancy, pesticide exposure and drug exposure in CHDs group and control group (P < 0.05). MTHFR rs1801133 was significantly associated with their offspring CHDs in mothers. The polymorphism of maternal MTHFR rs1801133 increased plasma HCY level, especially the homozygous mutation. Besides the environmental factors, our results suggested that the maternal MTHFR rs1801133 polymorphism might be a risk factor of their offspring CHDs, which may be due to the hyperhomocysteinemia by abnormal metabolism of HCY.

Highlights

Congenital heart diseases (CHDs) refers to abnormal cardiovascular structure or function at birth
Logistic regression analyses showed that methylenetetrahydrofolate reductase (MTHFR) rs1801133 was significantly increased their offspring CHDs risk compared with control group of mothers (Table 2)
In this study we found that gender of children, mothers’ child-bearing age, education, occupation, history of abortion, early pregnancy health, smoking, pesticide exposure and drug exposure were significantly associated with the risk of offspring CHDs susceptibility

Summary

Introduction

Congenital heart diseases (CHDs) refers to abnormal cardiovascular structure or function at birth. Monitoring data on birth defects in China showed that CHDs have been the highest incidence of birth defects and increased yearly since 2005 [1]. They became the first cause of death among 1 year. The relationship between the maternal plasma HCY level and SNPs of MTHFR was only showed a tendency without statistic significances. The objective of the present further study was to evaluate the relationship between the genotype and HCY level in the plasma of mothers with offspring CHDs by case–case study in a larger crowd, and a further investigation on maternal environmental risks and the genotype factor in MTHFR by case–control study

Objectives

Results

Conclusion