北京大学学报（医学版）2024，Vol.56Issue(3)：384-389,6.DOI:10.19723/j.issn.1671-167X.2024.03.002
转化生长因子β信号通路与非综合征型唇腭裂发病风险的基因-基因及基因-环境交互作用
Gene-gene/gene-environment interaction of transforming growth factor-β signaling pathway and the risk of non-syndromic oral clefts
摘要
Abstract
Objective:To explore the association between polymorphisms of transforming growth factor-β(TGF-β)signaling pathway and non-syndromic cleft lip with or without cleft palate(NSCL/P)among Asian populations,while considering gene-gene interaction and gene-environment interaction.Methods:A total of 1 038 Asian NSCL/P case-parent trios were ascertained from an international consortium,which conducted a genome-wide association study using a case-parent trio design to investigate the genes affec-ting risk to NSCL/P.After stringent quality control measures,343 single nucleotide polymorphism(SNP)spanning across 10 pivotal genes in the TGF-β signaling pathway were selected from the original genome-wide association study(GWAS)dataset for further analysis.The transmission disequilibrium test(TDT)was used to test for SNP effects.The conditional Logistic regression models were used to test for gene-gene interaction and gene-environment interaction.Environmental factors collected for the study in-cluded smoking during pregnancy,passive smoking during pregnancy,alcohol intake during pregnancy,and vitamin use during pregnancy.Due to the low rates of exposure to smoking during pregnancy and al-cohol consumption during pregnancy(＜3％),only the interaction between maternal smoking during pregnancy and multivitamin supplementation during pregnancy was analyzed.The threshold for statistical significance was rigorously set at P=1.46 × 10-4,applying Bonferroni correction to account for multiple testing.Results:A total of 23 SNPs in 4 genes yielded nominal association with NSCL/P(P＜0.05),but none of these associations was statistically significant after Bonferroni's multiple test correction.How-ever,there were 6 pairs of SNPs rs4939874(SMAD2)and rs1864615(TGFBR2),rs2796813(TGFB2)and rs2132298(TGFBR2),rs4147358(SMAD3)and rs1346907(TGFBR2),rs4939874(SMAD2)and rs1019855(TGFBR2),rs4939874(SMAD2)and rs12490466(TGFBR2),rs2009112(TGFB2)and rs4075748(TGFBR2)showed statistically significant SNP-SNP interaction(P＜1.46 × 10-4).In contrast,the analysis of gene-environment interactions did not yield any significant results after being cor-rected by multiple testing.Conclusion:The comprehensive evaluation of SNP associations and interac-tions within the TGF-β signaling pathway did not yield any direct associations with NSCL/P risk in Asian populations.However,the significant gene-gene interactions identified suggest that the genetic architec-ture influencing NSCL/P risk may involve interactions between genes within the TGF-β signaling path-way.These findings underscore the necessity for further investigations to unravel these results and further explore the underlying biological mechanisms.关键词
非综合征型唇腭裂/转化生长因子β信号通路/全基因组关联研究/核心家系Key words
Non-syndromic cleft lip with or without cleft palate/Transforming growth factor-β signaling pathway/Genome-wide association study/Case-parent trio分类
医药卫生引用本文复制引用
侯天姣,秦雪英,武轶群,郑鸿尘,李静,吴涛,朱洪平,周治波,王竹青,王梦莹,王斯悦,彭和香,郭煌达,李奕昕,章涵宇..转化生长因子β信号通路与非综合征型唇腭裂发病风险的基因-基因及基因-环境交互作用[J].北京大学学报（医学版）,2024,56(3):384-389,6.基金项目
国家自然科学基金(81573225)Supported by the National Natural Science Foundation of China(81573225) （81573225）
