title: Meta-Analysis-Based Preliminary Exploration of the Connection between ATDILI and Schizophrenia by GSTM1/T1 Gene Polymorphisms.
abstract: Anti-tuberculosis drugs have some adverse effects such as anti-tuberculosis drug-induced liver injury (ATDILI) and mental disorders. The involvement of glutathione S-transferase (GST) genes in pathogenesis of ATDILI or schizophrenia (SCZ) has been reported. Therefore, GST genes may exemplify molecular connectors between ATDILI and SCZ. However, association studies of GSTM1/T1 polymorphisms with these two diseases have yielded conflicting results. After searching case-control association studies in PubMed, ISI Web of Science, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and Chinese BioMedical Literature Database, we performed meta-analyses across a total of 20 published association studies on 3146 subjects for the association of GSTM1 and ATDILI, 2587 for the GSTT1-ATDILI association, 2283 for GSTM1-SCZ and 1116 for GSTT1-SCZ to test the associations of GSTM1/T1 polymorphisms with ATDILI and SCZ. The GSTM1 present genotype was significantly associated with decreased risks of ATDILI (risk ratio(RR): 0.81, 95% confidence interval (CI): 0.75-0.88, P < 0.0001) and SCZ (RR: 0.88, 95%CI: 0.80-0.96, P = 0.004) according to the fixed-effect model, while the GSTT1 present genotype was significantly associated only with a high risk of SCZ (RR: 1.17, 95%CI: 1.04-1.32, P = 0.01) according to both the random- and fixed-effect models, but not with ATDILI (P = 0.82) according to the fixed-effect model. Moreover, these significant results were supported with moderate evidence according to the Venice criteria. These results indicate that GSTM1 represents a genetic connection between ATDILI and SCZ, and suggest that ATDILI and SCZ may be co-occurring for the subjects with GSTM1 null genotype.
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiaotong University, Shanghai, 200030, China; Shanghai Mental Health Center, Shanghai Jiaotong University, Shanghai, 200240, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cai
authors.affiliation: School of Medicine, Shanghai Jiaotong University, Shanghai, 200020, China.
authors.forename: Mei-Hong
authors.initials: MH
authors.lastname: Cai
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
authors.forename: Mei-Yan
authors.initials: MY
authors.lastname: Wang
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiaotong University, Shanghai, 200030, China; Shanghai Mental Health Center, Shanghai Jiaotong University, Shanghai, 200240, China.
authors.forename: Yi-Feng
authors.initials: YF
authors.lastname: Xu
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiaotong University, Shanghai, 200240, China.
authors.forename: Wen-Zhong
authors.initials: WZ
authors.lastname: Chen
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiaotong University, Shanghai, 200030, China; Shanghai Mental Health Center, Shanghai Jiaotong University, Shanghai, 200240, China.
authors.forename: Shen-Ying
authors.initials: SY
authors.lastname: Qin
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiaotong University, Shanghai, 200030, China; Shanghai Mental Health Center, Shanghai Jiaotong University, Shanghai, 200240, China.
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Wan
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiaotong University, Shanghai, 200030, China; Shanghai Mental Health Center, Shanghai Jiaotong University, Shanghai, 200240, China.
authors.forename: Lin
authors.initials: L
authors.lastname: He
mesh_terms: D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D016208:Databases, Factual; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1