中文摘要：

目的：探索中国人群中细胞黏附相关基因多态性与非综合征型唇裂合并或不合并腭裂（isolated nonsyndromic cleft lip with or without cleft palate,NSCL/P）的关联关系及可能存在的基因-环境交互作用。方法：对一项国际多中心的全基因组关联研究（genome-wide association study,GWAS）的数据进行再分析,选取其中806个中国人群NSCL/P核心家庭,对该人群的8个细胞黏附相关基因包括CDH1、CTNNB1、PVRL1、PVRL2、PVRL3、ACTN1、VCL、LEF1进行了传递不平衡检验（transmisssion diseqilibrium test,TDT）及基因-环境交互作用分析。环境因素包括患儿母亲孕期吸烟、被动吸烟、饮酒及服用多种维生素。结果：经数据质量控制后,共纳入226个单核苷酸多态性（single nucleotide polymorphisms,SNPs）位点,TDT结果显示,CTNNB1、CDH1、ACTN1基因中有23个SNPs与NSCL/P之间存在关联（P〈0.05）,但经Bonferroni校正后,这些关联均无统计学意义（P〉0.000 2）。基因-环境交互作用的分析结果显示,14号染色体的ACTN1基因中rs743127位点与母亲孕期被动吸烟的交互作用具有统计学意义（P=0.000 1）,母亲孕期无被动吸烟时携带一个该危险位点的患儿的OR值为0.59（95%CI：0.38-0.90）,患儿母亲孕期中有被动吸烟情况时携带一个危险位点的患儿的OR值为2.00（95%CI：1.23-3.26）。而ACTN1基因的rs1475034、rs370535、rs2273419位点、CTNNB1基因的rs106871位点与被动吸烟和PVRL3基因的rs7634000、rs2971366、rs2634553、rs1489032、rs7624812位点与母亲孕期补充维生素的交互作用并无统计学意义（P〉0.000 2）。结论：传递不平衡检验未发现所纳入的细胞黏附相关基因多态性与NSCL/P存在关联,但基因-环境交互作用分析结果提示,ACTN1基因可能通过基因-环境交互作用而影响NSCL/P的发病风险。

英文摘要：

Objective： To explore the association and gene-environment interaction between single nucleotide polymorphisms（ SNPs） involved in cell-cell adhesion and non-syndromic cleft lip with or without cleft palate（ NSCL / P） among Chinese population. Methods： A total of 806 NSCL / P trios were drawn by an international consortium,which conducted a genome-wide association study（ GWAS） using a caseparent trio design to investigate genes affecting risks to NSCL / P. The transmission disequilibrium test（ TDT） was used to explore the association between cell-cell adhesion genes,including CDH1,CTNNB1,PVRL1,PVRL2,PVRL3,ACTN1,VCL,LEF1,and NSCL / P. Conditional Logistic regression models were used to estimate effects on risk of exposed and unexposed children. Four common maternal exposures including maternal smoking,environmental tobacco smoke,alcohol consumption and multivitamin supplementation during pregnancy were included in this study. Results： A total of 226 SNP markers were tested after quality control in this study. Although 23 SNPs in three genes（ CTNNB1,CDH1,ACTN1） showed nominal significant association with NSCL / P in the TDT（ P〈0. 05）. There were no significant evidence of linkage and association that remained in the transmission disequilibrium test after Bonferroni correction（ P〈0. 000 2）. Tests for gene-environment interaction yielded significant results between rs743127 in ACTN1 and environmental tobacco smoke（ P = 0. 000 1） with an estimated OR（ case ｜ G and E） = 2. 00（ 95% CI： 1. 23- 3. 26） and OR（ case ｜ G no E） = 0. 59（ 95% CI： 0. 38-0. 90）. Among the lower P value results in gene-environment tests,there were no significant results between rs1475034,rs370535,rs2273419 in ACTN1,rs106871 in CTNNB1 and environmental tobacco smoke interaction. There were also no significant results between rs7634000,rs2971366,rs2634553,rs1489032,rs7624812 in PVRL3 and multivitamin supplementation during pregnancy in gene-environment tests（ P〈0. 000 2）. Conclus