Association of BHMT and BHMT2 gene polymorphisms with non-syndromic congenital heart disease: a case-control study
10.3760/cma.j.cn112150-20231025-00292
- VernacularTitle:BHMT和 BHMT2基因多态性与单纯性先天性心脏病关联的病例对照研究
- Author:
Jiapeng TANG
1
;
Jun OU
;
Yige CHEN
;
Mengting SUN
;
Manjun LUO
;
Qian CHEN
;
Taowei ZHONG
;
Jianhui WEI
;
Tingting WANG
;
Jiabi QIN
Author Information
1. 中南大学湘雅公共卫生学院流行病与卫生统计系，长沙 410078
- Keywords:
Heart defects, congenital;
Human betaine-homocysteine methyltransferase gene;
Case-control studies;
Haplotype;
Interaction
- From:
Chinese Journal of Preventive Medicine
2024;58(4):497-507
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the association of human betaine-homocysteine methyltransferase ( BHMT) and BHMT2 gene polymorphisms with non-syndromic congenital heart disease (CHD). Methods:A hospital-based case-control study was conducted, in which children with CHD who attended Hunan Children′s Hospital from January 2018 to May 2019 were enrolled as the case group, and children without any congenital deformity who attended the hospital during the same period were enrolled as the control group on a 1∶1 basis. A self-administered questionnaire survey was performed to collect information about the study subjects and their mothers, and then venous blood samples were collected from the subjects to detect BHMT and BHMT2 gene polymorphisms. Logistic regression analyses were used to evaluate the association of BHMT and BHMT2 gene polymorphisms and their haplotypes with CHD. Crossover analyses and logistic regression were used to explore the gene-gene and gene-environment interactions. Results:The case and control group both enrolled 620 children. The multivariate logistic regression showed that BHMT gene polymorphisms at rs3733890 (AA vs. GG: OR=3.476, Q FDR<0.001; GA vs. GG: OR=1.525, Q FDR=0.036), at rs1915706 (CC vs. TT: OR=3.464, Q FDR<0.001) and at rs1316753 (GG vs. CC: OR=1.875, Q FDR=0.020) increased the risk of CHD. Children with haplotype of A-G-A had an increased risk of CHD ( OR=1.468, 95% CI: 1.222-1.762). Interaction analysis showed that a statistically significant positive interaction between rs3733890 and rs1915706 on both additive ( RERI=0.628, 95% CI: 0.298-0.958) and multiplicative ( OR=3.754, 95% CI: 1.875-7.519) scales. Gene-environment interactions were found between the BHMT gene with secondhand smoke exposure before pregnancy and in early pregnancy, tea consumption before pregnancy and in early pregnancy, alcohol consumption before pregnancy, and folic acid supplementation before or during pregnancy. Conclusion:BHMT gene rs3733890, rs1915706 and rs1316753 polymorphisms may be associated with the risk of CHD. In addition, there is an association of cooperative interaction between rs3733890 and rs1915706 on both additive and multiplicative scales with the risk of CHD, and the BHMT gene interacts with multiple environmental factors.
