title: Analysis of IL-6, STAT3 and HSPA1L gene polymorphisms in anti-tuberculosis drug-induced hepatitis in a nested case-control study.
abstract: OBJECTIVE
  To investigate the association of IL-6, STAT3 and HSPA1L polymorphisms with the risk of anti-tuberculosis drug-induced hepatitis (ATDH) in Chinese Han population.
  
  
  METHODS
  The study was designed as a nested case-control study within a prospective cohort. Each case was matched with four controls by sex, age at baseline (±5 years), treatment history, disease severity, drug dosage and place of sample collection. Genetic polymorphisms of IL-6, STAT3 and HSPA1L were determined blindly by TaqMan single-nucleotide polymorphism (SNP) genotyping assay. Odds ratio (OR) with 95% confidence intervals (CIs) was estimated by conditional logistic regression model to measure the association between selected SNPs and the risk of ATDH.
  
  
  RESULTS
  A total of 89 incident ATDH cases and 356 ATDH-free controls were genotyped for IL-6 (rs2066992, rs2069837, rs1524107), STAT3 (rs1053004, rs1053023, rs1053005) and HSPA1L (rs2227956). In genotype analysis, no significant difference was observed in genotypes frequencies of the seven selected SNPs between case and control group after Bonferroni correction. In haplotype analysis, carriers with STAT3 GAT and AGC (rs1053023-rs1053005-rs1053004) haplotypes had a significantly higher risk of ATDH compared with wild-type haplotype (P<0.0001).
  
  
  CONCLUSIONS
  This study suggested that genetic variants of STAT3 might contribute to ATDH susceptibility in Chinese Han population. Studies in larger, varied populations are required to confirm these findings.
authors: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
authors: Jing
authors: J
authors: Wang
authors: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
authors: Ru
authors: R
authors: Chen
authors: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China; Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Shaowen
authors: S
authors: Tang
authors: Clinical Research Division, Peking University Institute of Mental Health, and Key Laboratory for Mental Health, Ministry of Health, Beijing, China.
authors: Xiaozhen
authors: X
authors: Lv
authors: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
authors: Shanshan
authors: S
authors: Wu
authors: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.
authors: Yuan
authors: Y
authors: Zhang
authors: Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors: Yinyin
authors: Y
authors: Xia
authors: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
authors: Pei
authors: P
authors: Gao
authors: Department of Tuberculosis Treatment, Beijing Institute for Tuberculosis Control, Beijing, China.
authors: Dehua
authors: D
authors: Tu
authors: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
authors: Dafang
authors: D
authors: Chen
authors: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
authors: Siyan
authors: S
authors: Zhan
mesh_terms: D000995:Antitubercular Agents / Q000009:adverse effects*; D044466:Asian People; D016022:Case-Control Studies; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006505:Hepatitis / Q000209:etiology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D050796:STAT3 Transcription Factor / Q000235:genetics*
chemical_list: D000995:Antitubercular Agents; D018840:HSP70 Heat-Shock Proteins; C543454:HSPA1L protein, human; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human