叉生分析在基因-环境因素交互作用中应用  

Interactive effects of gene-environment on congenital heart disease: a crossover analysis

作　　者：刘一志[1] 李栋[1] 郭淼[2] 纪龙[1] 程琮[1] 

机构地区：[1]泰山医学院流行病学研究所 [2]泰山医学院生物科学学院

出　　处：《中国公共卫生》2015年第4期458-460,共3页Chinese Journal of Public Health

基　　金：山东省自然科学基金(ZR2011HM018)

摘　　要：目的应用叉生分析法分析先天性心脏病(CHD)基因与环境因素的交互作用,为CHD的病因研究提供新的分析方法。方法采用以医院为基础的病例对照研究方法,对2012年7月—2013年10月在山东省4家医院胸外科住院的137例CHD患儿及同期住院的132例无CHD及其他畸形的其他疾病患儿母亲进行问卷调查,并采集患儿空腹外周静脉血进行DNA提取和基因检测;应用叉生分析方法分析CHD致病基因(MTHFRC677T位点突变)与环境因素(孕期患病情况)的交互作用。结果病例组和对照组患儿CC、CT、TT基因型分别占20.44%和36.36%、38.69%和40.91%、40.87%和22.73%,C、T等位基因分别占39.78%和57.58%、60.22%和42.42%,2组患儿全基因型、等位基因频率比较,差异均有统计意义(P<0.010);叉生分析显示,CHD致病MTHFR基因C677T位点突变与环境因素(孕期患病情况)基于相加模型的交互作用差异有统计学意义(U=2.060,P=0.020),各评价指标:SI=4.85,AP=70%,AP*=79%,RERI=5.64;基于相乘模型交互作用差异无统计学意义(P>0.05)。结论 MTHFR基因C677T位点突变与孕期患病对CHD具有相加交互作用。Objective To analyze gene-environment interactive effects on congenital heart disease（CHD） with crossover analysis and to provide a new method for etiological research of CHD. Methods Using hospital-based casecontrol design and questionaire survey,137 mothers of children with CHD and 132 of children with diseases other than CHD or congenital malformation hospitalized in department of thoracic surgery in four hospitals during the period of July2012 through October 2013 were investigated. The fasting peripheral venous blood samples of the children were collected for DNA extraction and gene detection. Crossover analysis was adopted to assess interactive effects of CHD gene（M THFR C677 T mutation） and environment（pregnant morbidity of the mothers）. Results There were significant differences in the percentages of genotypes of CC（20. 44% vs. 36. 36%）,CT（38. 69% vs. 40. 91%）,and TT（40. 87% vs. 22. 73%）and of allees of C（39. 78% vs. 57. 58%） and T（60. 22% vs. 42. 42%） betw een the cases and the controls（P 〈0. 010 for all）. Crossover analysis show ed that there was a statistically significant interaction betw een CHD pathogenic MTHFR gene C677 T mutation and environmental factors（maternal morbidity） based on the additive model（U = 2. 060,P = 0. 020）,with the evaluation indexes of synergy index（SI） of 4. 85,attributable proportion（AP） of 70%,AP＊of79%,and relative excess risk due to interaction（RERI） of 5. 64. But no significant interaction was observed based on the results of multiplicative model（P〉 0. 05）. Conclusion There is an additive interaction betw een CHD MTHFR C677 T gene mutation and maternal morbidity for incidence of CHD.

关 键 词：先天性心脏病(CHD) MTHFR基因 环境因素 交互作用 叉生分析 

分 类 号：R541[医药卫生—心血管疾病]