中文摘要：

目的：：探索中国人群中转化生长因子β（ transforming growth factor-β, TGFB）信号通路基因多态性与非综合征型唇腭裂（ non-syndromic oral clefts, NSOC）的关联关系及可能存在的基因环境交互作用。方法：在806个中国汉族人群非综合征型唇裂合并或不合并腭裂（ non-syndromic cleft lip with or without cleft palate, NSCL/P）核心家系中,对TGFB信号通路上的10个基因进行了传递不平衡检验以及基因环境交互作用分析。环境因素包括母亲孕早期吸烟、被动吸烟、饮酒及补充多维生素制剂。结果：经过质量控制的筛选,共对343个位点的单核苷酸多态性（ single nucleotide polymorphisms, SNPs）进行了传递不平衡检验及交互作用分析,结果显示,共有6个基因中的19个SNPs与NSCL/P之间存在关联（P〈0.05）,但经过Bonferroni校正后,这些关联均不具有统计学意义。经多重检验校正后,未发现常见孕期环境暴露因素与TGFB信号通路上的基因多态性存在有统计学意义的基因环境交互作用。结论：未发现TGFB信号通路上的基因多态性与NSCL/P之间存在关联。

英文摘要：

Objective：To explore the association between 10 candidate genes on transforming growth fac-tor-β （ TGFB） signaling pathway and non-syndromic cleft lip with or without cleft palate （ NSCL/P） among Chinese populations, and to study the gene-environment interaction. Methods：A total of 806 Chinese Han NSCL/P trios were ascertained from an international consortium, which conducted a genome-wide associa-tion study using a case-parent trio design to investigate the genes affecting risk to NSCL/P. The transmis-sion disequilibrium test （ TDT） was used to test for effects of 343 single nucleotide polymorphisms （ SNPs） in 10 genes on TGFB signaling pathway including DCN, TGFB1, TGFB2, TGFB3, TGFBR1, TGFBR2, BAMBI, SMAD2, SMAD3 and SMAD4. The conditional regression models were used to test for gene-envi-ronment interaction. Results： For TDT, although 19 SNPs showed nominal significant association with＆amp;nbsp;NSCL/P, no significant evidence of association was seen for all SNPs in 806 NSCL/P trios after Bonferroni correction. The interactions between genes and maternal smoking, environmental tobacco smoke, alcohol consumption and multi-vitamin supplementation during pregnancy did not attain statistical significance after correction for multiple comparisons. Conclusion：No evidence for SNP effect of genes on TGFB signaling pathway and significant gene-environment interaction was seen in our data.