BMP4、TGF-β3基因多态性与环境暴露在非综合征性唇腭裂发生中的交互作用

The correlation analysis between environmental factors, bone morphogenetic protein-4 and transforming growth factor beta-3 polymorphisms in nonsyndromic cleft lip with or without cleft palate

目的 探讨环境暴露因素、骨形态生成蛋白4（BMP4）基因、转化生长因子β3（transforming growth factor beta-3,TGF-β3）基因之间的交互作用在非综合征性唇腭裂（nonsyndromic cleft lip and cleft palate,NSCLP）发生中的可能作用.方法 通过问卷调查获取环境暴露资料.用聚合酶链反应（PCR）-限制性片段长度多态性（restriction fragment length polymorphism,RFLP）技术对对照组（200例）和NSCLP组（200例）各基因位点的多态性进行检测.采用多因子降维法（multifactor djmensionality reduction,MDR）分析基因之间、基因与环境之间的交互作用关系,并对筛选的交互作用关系用Logistic回归进行验证.结果 BMP4 T538C、TGF-β3 C641A和TGF-β3G15572-三个单核苷酸多态性（single nucleotide polymorphism,SNP）位点间的交互作用与NSCLP的发生无关联.基因与环境交互作用分析发现,BMP4 T538C与母亲妊娠早期被动吸烟、母亲妊娠早期感染史对NSCLP的发生具有交互作用 TGF-β3G15572-与母亲妊娠早期被动吸烟、母亲妊娠早期感染史、父亲知晓妊娠前吸烟、父亲知晓妊娠前饮酒、母亲妊娠早期补充维生素对NSCLP的发生具有交互作用.经Logistic回归验证,结果一致.结论 NSCLP是基因与环境因素共同作用的结果,易感基因多态性影响着个体对环境因素的反应,研究它们之间的相互关系对阐明NSCLP的病因及发病机制具有重要意义.

Objective To investigate the effects of interactions among environmental factors, bone morphogenetic protein-4 （ BMP4 ） and transforming growth factor beta-3 （ TGF-β3 ） polymorphisms on nonsyndromic cleft lip and cleft palate （NSCLP） . MethodsThe data of environmental exposures were collected with questionnaires.Genotypes were determined with techniques of polymerase chain reactionrestriction fragment length polymorphism. Interactions between genes, environmental factors and NSCLP were analyzed using multifactor dimensionality reduction （MDR） method. The interactions were validated by logistic regression analysis. ResultsThere was no correlation between three single nucleotide polymorphism （SNP） associated with NSCLP. The developmental accident of NSCLP had higher risk in the interaction between BMP4 T538C, maternal passive smoking and infection in first trimester pregnancy, as well as in the interaction of six factors between TGF-β3 G15572-, maternal passive smoking, infections, multivitamin supplement in the first trimester pregnancy, paternal smoking and high risk drinking before realizing pregnancy than in other interactions of environmental factors. The results could be validated by logistic regression analysis.Conclusions The NSCLP is induced by the interactions between genes and environmental risk factors.