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。

Objective：To explore the association between 10 candidate genes on transforming growth factor-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 association study using a case-parent trio design to investigate the genes affecting risk to NSCL/P. The transmission 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-environment interaction. Results: For TDT, although 19 SNPs showed nominal significant association with 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.