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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。
Objective: To explore the association between cell adhesion-related gene polymorphism and non-cleft lip with or without cleft palate (NSCL / P) in Chinese population and possible gene-environment interaction effect. METHODS: The data of an international multicenter genome-wide association study (GWAS) were reanalyzed. Among them, 806 Chinese NSCL / P core families were selected and 8 cell adhesion-related genes Including CDH1, CTNNB1, PVRL1, PVRL2, PVRL3, ACTN1, VCL and LEF1, were tested for TDT and gene-environment interaction. Environmental factors include smoking mothers during pregnancy, passive smoking, drinking and taking multivitamins. Results: A total of 226 single nucleotide polymorphisms (SNPs) sites were identified after data quality control. TDT results showed that there were 23 SNPs in CTNNB1, CDH1 and ACTN1 genes and NSCL / P (P <0.05), but after Bonferroni correction, these associations were not statistically significant (P> 0.000 2). The analysis of gene-environment interaction showed that the interaction between rs743127 in ACTN1 gene on mother chromosome 14 and passive smoking in mother during pregnancy was statistically significant (P = 0.000 1). The mother carried a risk of passive smoking during pregnancy The odds ratio was 0.59 (95% CI: 0.38-0.90). The odds ratio (OR) of children with a dangerous site during passive smoking in their mothers was 2.00 (95% CI: 1.23-3.26 ). There was no significant difference in the interaction between ACT14 gene rs1475034, rs370535, rs2273419, CTNNB1 rs106871 and passive smoking and PVRL3 rs7634000, rs2971366, rs2634553, rs1489032, rs7624812 and mothers’ vitamin supplementation during pregnancy (P < P> 0.000 2). CONCLUSIONS: Transmission disequilibrium test found no association between NSCL / P and NSCL / P. However, the results of gene-environment interaction analysis suggest that ACTN1 may affect NSCL / P through gene-environment interaction Risk of onset.