中国汉族人群谷胱甘肽硫转移酶M1及T1基因多态性与先天性心脏病发病风险的关系

目的探讨中国汉族人群谷胱甘肽硫转移酶(glutathione S-transferases,GST)M1及T1基因(GSTM1/GSTT1)多态性与先天性心脏病(先心病)发病风险的关系。方法采用病例-对照研究(病例组365例,对照组372例),运用多重聚合酶链反应检测先心病患者及健康对照GSTM1/GSTT1基因型;并利用多因素非条件logistic回归模型,进行先心病发病风险影响因素关联强度及交互作用分析。结果 GSTM1/GSTT1基因多态性及研究对象母亲围孕期吸烟、饮酒、化学物质接触、孕前体质量指数、教育程度、定期产检以及怀孕知情时间在病例组和对照组之间分布存在明显差异(P<0.05)。GSTM1/GSTT1基因缺失与先心病发病风险显著正相关(OR=1.56,P=0.049;OR=1.73,P=0.036)。经logistic回归分析,GSTM1(-)/GSTT1(-)基因型和研究对象母亲围孕期吸烟、饮酒、化学物质接触以及孕前高体质量指数是先心病发病的高危因素,研究对象母亲围孕期定期产检以及摄入充足的叶酸是先心病的保护因素。研究对象母亲围孕期吸烟与GSTM1(-)/GSTT1(-)基因型之间具有正相加交互作用,与母亲围孕期不吸烟且GSTM1/T1基因未缺失的研究对象相比,其母亲围孕期吸烟且携带GSTM1(-)和(或)GSTT1(-)基因型的先心病发病风险显著上升(OR=9.01,3.87,3.01;95%CI:1.73～39.69,1.21～19.57,1.13～9.69)。结论 GSTM1/GSTT1基因缺失是先心病发病风险的独立危险因素;GSTM1(-)/GSTT1(-)基因型与孕母围孕期吸烟在先心病的发生中具有协同作用。

Association of glutathione S-transferases M1 and T1 genomic polymorphisms with risk of congenital heart disease in Chinese Han population

Objectives To investigate the correlation between glutathione S-transferases （GST） M1 and T1 genomic polymorphisms with risk of congenital heart disease （CHD） in Chinese Han population. Methods We did a case-control study （case=365 ,control=372）. The GSTM1 and GSTI＇I genotype distribution was analyzed by multiplex polymerase chain reaction, and multi-factors non-conditional logistic regression analysis was also used to analyze the correlation and interaction of the factors. Results There were significant differences between case and control groups in GSTM1/GSTT1 genotypes, mother＇s smoking habits during gestation, drinking, exposure to harmful substances, body mass index （BMI） before pregnancy, education of gestational mother, regular prenatal examination and informed duration of pregnancy （P〈 0.05）. GSTM1 （-） and GSTT1 （-） genotypes were positively related to CHD （OR =1.56,P=0.049 ; OR =1.73, P= 0.036）. By using multi-factors non-conditional logistic regression analysis, we found that GSTM1 （-） and GSTT1 （-） genotypes, mother＇s smoking habits during gestation, drinking, maternal exposure to harmful substances and BMI before pregnancy were risk factors of CHD, while regular prenatal examination and folate intake were protection factors. The interaction analysis suggested positive additive interactions between mother＇s smoking habits during gestation and GSTM1 （-）/GSTF1 （-） genotypes. The CHD risk of such subjects who carried GSTM1 （-） and/or GSTT1 （-） genotypes were dramatically increased （OR=9.01, 3.87, 3.01, 95%CI： 1.73-39.69, 1.21-19.57, 1.13-9.69）. Conclusions GSTM1/GSTT1 gene deletions are independent risk factors for CHD. There is an interaction between mother＇s smoking habits during gestation and GSTM1 （-）/GSTY1 （-） genotypes in the occurring of CHD.