精神分裂症和抗结核药物所致肝损伤共同致病基因的筛选与验证

发布时间：2018-03-27 08:05

本文选题：精神分裂症　切入点：抗结核药物所致肝损伤　出处：《中国神经精神疾病杂志》2017年02期

【摘要】：目的筛选并验证抗结核药物所致肝损伤(anti-tuberculosis drug-induced hepatotoxicity,ATDH)与精神分裂症(schizophrenia,SCZ)之间可能的共同致病基因。方法通过查询基因数据库及文献,分别确定ATDH和SCZ的致病基因,利用重启动随机游走(integrating network random walk with restart,RWR)、基因富集分析(gene set enrichment analysis,GSEA)和超几何检验等生物信息学分析技术筛选出两种疾病的可能共同致病基因,建立定期更新的两种疾病共同致病基因在线数据库(www.bio-x.cn/atdh-sczgenes.html),查阅文献以进一步筛选与ATDH和SCZ都有关的基因;利用meta分析等方法验证候选基因,以最终确定共同致病基因。结果经信息学分析技术筛选,共获得500个候选共同致病基因。进一步经文献检索,得到GSTM1和GSTT1基因为候选共同致病基因并纳入meta分析。Meta分析显示,GSTM1基因同ATDH(P=0.01)和SCZ(P0.01)相关均有统计学意义;而GSTT1基因同ATDH和SCZ的发病风险关系均无统计学意义(P0.05)。结论 GSTM1基因为ATDH和SCZ的共同致病基因。
[Abstract]:Objective to screen and verify the possible co-pathogenic genes between anti-tuberculosis-induced liver injury and drug-induced hepatotoxity (ATDH) and schizophrenia. Methods the pathogenetic genes of ATDH and SCZ were identified by querying the gene database and literature. The possible co-pathogenic genes of the two diseases were screened by using the bioinformatics analysis techniques such as restarting random walk network random walk with restartr, gene set enrichment analysis and hypergeometric test. To establish a regularly updated online database of common pathogenicity genes of two diseases, www.bio-x.cnratdh-sczgenes.html.com, to review the literature to further screen genes related to both ATDH and SCZ, and to verify candidate genes by meta analysis, etc. Results A total of 500 candidate co-pathogenic genes were obtained by informatics analysis. GSTM1 and GSTT1 gene were obtained because of the candidate co-pathogenic genes and included in meta analysis. Meta-analysis showed that there was a significant correlation between GSTM1 gene and ATDHH-P0. 01) and SCZG P0. 01). There was no significant correlation between GSTT1 gene and the risk of ATDH and SCZ. Conclusion the GSTM1 gene is the common pathogenic gene of ATDH and SCZ.
【作者单位】：上海交通大学Bio-X研究院上海交通大学医学院附属精神卫生中心"遗传发育与精神神经疾病"教育部重点实验室上海精神疾病重点实验室(编号:13dz2260500);中国科学院上海生命科学研究院健康科学研究所;上海交通大学生命科学技术学院;
【分类号】：R749.3

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