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  

Association of BHMT and BHMT2 gene polymorphisms with non-syndromic congenital heart disease:a case-control study

作　　者：唐嘉鹏 欧军 陈羿戈 孙梦婷 罗曼君 陈倩 钟韬玮 魏剑晖 王婷婷 秦家碧 Tang Jiapeng;Ou Jun;Chen Yige;Sun Mengting;Luo Manjun;Chen Qian;Zhong Taowei;Wei Jianhui;Wang Tingting;Qin Jiabi(Department of Epidemiology and Health Statistics,Xiangya School of Public Health,Central South University,Changsha 410078,China)

机构地区：[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

出　　处：《中华预防医学杂志》2024年第4期497-507,共11页Chinese Journal of Preventive Medicine

基　　金：国家自然科学基金项目(82073653、81803313);湖南省杰出青年基金项目(2022JJ10087)。

摘　　要：目的:探讨人甜菜碱同型半胱氨酸甲基转移酶( BHMT)和 BHMT2基因多态性与单纯性先天性心脏病(CHD)的关联。 方法:采用基于医院的病例对照研究,选取2018年1月至2019年5月在湖南省儿童医院就诊的先天性心脏病患儿作为病例组,按1∶1选取同时期在该院就诊并排除任何先天畸形的儿童作为对照组。通过自制的问卷收集研究对象及其母亲的相关信息并在完成调查后采集儿童静脉血用于 BHMT、BHMT2基因多态性的检测。采用logistic回归分析 BHMT、BHMT2基因多态性以及单倍型与CHD的关联,并采用叉生分析和logistic回归分析探讨基因-基因、基因-环境的交互作用。 结果:纳入病例组和对照组各620例患儿。多因素logistic回归显示, BHMT基因rs3733890位点(AA vs GG: OR=3.476, Q FDR<0.001;GA vs GG: OR=1.525, Q FDR=0.036)、rs1915706位点(CC vs TT: OR=3.464, Q FDR<0.001)和rs1316753位点(GG vs CC: OR=1.875, QFDR=0.020)增加了CHD发生风险。携带单倍型A-G-A的患儿CHD风险增加( OR=1.468,95% CI:1.222~1.762)。交互作用分析显示,rs3733890和rs1915706这2个位点在相加( RERI=0.628,95% CI:0.298~0.958)和相乘( OR=3.754,95% CI:1.875~7.519)维度均呈正向交互作用。 BHMT基因与孕前、孕早期二手烟暴露和饮茶、孕前饮酒以及孕前或孕期叶酸服用存在交互作用。 结论:BHMT基因rs3733890、rs1915706和rs1316753多态性与CHD的发病可能有关。此外,rs3733890和rs1915706这2个位点对CHD发病存在相加和相乘维度的协同交互作用,且 BHMT基因与多种环境因素存在交互作用。ObjectiveTo explore the association of human betaine-homocysteine methyltransferase(BHMT)and BHMT2 gene polymorphisms with non-syndromic congenital heart disease(CHD).MethodsA 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.ResultsThe 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 in

关 键 词：心脏缺损 先天性 人甜菜碱同型半胱氨酸甲基转移酶基因 病例对照研究 单倍型 交互作用 

分 类 号：R725.4[医药卫生—儿科]