结合吸烟与遗传因素交互作用鉴定骨质疏松症易感基因  

Identification of susceptibility genes for osteoporosis through interaction between smoking and genetic factors

作　　者：杨波[1] 陈晓峰[2] 段媛媛[2] 郭燕[2] YANG Bo;CHEN Xiao-feng;DUAN Yuan-yuan;GUO Yan(Department of Orthopedics,Shaanxi Provincial People＇s Hospital,Xi an 710068;School of Life Science and Technology,Xi＇an Jiaotong University,Xi＇an 710049,China)

机构地区：[1]陕西省人民医院骨科,陕西西安710068 [2]西安交通大学生命科学与技术学院,生物医学信息工程教育部重点实验室,陕西西安710049

出　　处：《西安交通大学学报（医学版）》2018年第4期589-596,共8页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.31471188); 陕西省自然科学基础研究计划项目(No.2016JQ3026)

摘　　要：目的系统分析吸烟与骨质疏松症间的交互作用,挖掘互作基因,阐明吸烟影响骨质疏松症的功能机制。方法整合基因表达谱数据,通过双因素方差分析挖掘吸烟和骨质疏松症遗传因素互作基因,并结合通路富集分析挖掘功能性骨相关代谢通路。利用GWAS芯片,通过基因环境互作分析验证功能通路内互作基因,最后利用蛋白网络分析发掘互作基因参与的核心调控网络。结果表达谱分析鉴定了441个同时与吸烟和骨质疏松症密切相关的风险基因;通路富集分析揭示了吸烟调控骨质疏松症的潜在关键代谢通路—间隙连接;通过全基因组基因环境互作分析,我们验证了多个潜在关键风险基因,并且通过蛋白网络分析揭示了1个包含13个蛋白的潜在吸烟骨质疏松症互作核心调控网络。结论本研究发现了1个潜在的吸烟影响骨质疏松症的分子调控模型,对于相关疾病机制认识及后续药物靶点开发提供了新思路。Objective To make a systematic analysis of the interaction between osteoporosis and smoking to elucidate the molecular mechanisms underlying osteoporosis susceptibility affected by smoking.Methods First,a two-way ANOVA analysis was conducted using microarray data to search all potential genes associated with both smoking and osteoporosis.We further explored the potential biologically related metabolic pathways through gene pathway enrichment analysis.Then the interaction genes within enriched pathways were verified by genome-wide gene-environment interaction analysis.Finally,protein-protein interaction analysis was applied to identify the core regulatory network in which those verified genes involved.Results We identified441 risk genes closely associated with both smoking and osteoporosis by microarray analysis.Through gene pathway analysis,we identified a vital metabolism pathway,gap junction,which is a potential mediator between smoking and osteoporosis process.Finally,we verified some critical genes by genome-wide gene-environment interaction analysis,and revealed a potential smoking-osteoporosis interaction core regulatory network that included 13 proteins by protein network analysis.Conclusion We have discovered a new regulatory framework connecting smoking and osteoporosis,which provides new clues about disease etiologies and novel promising drug targets.

关 键 词：骨质疏松 吸烟 基因表达谱 双因素方差分析 基因环境互作 间隙连接 

分 类 号：R580[医药卫生—内分泌]