title: Interleukin-4 and interleukin-10 polymorphisms and antituberculosis drug-induced hepatotoxicity in Chinese population.
abstract: OBJECTIVE
  Evidence demonstrates that the delicate balance between pro- and anti-inflammatory cytokines determines the further progress to severe injury or recovery. Therefore, understanding which cytokines are associated with the development of drug-induced hepatotoxicity (DIH) might guide the prevention and therapeutic direction. Some polymorphisms of cytokine genes have been reported to be associated with DIH involving interleukin-4 (IL-4), interleukin-10 (IL-10) and tumour necrosis factor-α (TNF-α); however, these studies are still scanty with inconsistent results. In addition, most of these associations have not been investigated in antituberculosis drug-induced hepatotoxicity (ATDH) patients with the exception of TNF-α polymorphisms. Therefore, we aimed to investigate the association between IL-4 and IL-10 gene polymorphisms with the risk of ATDH in a Chinese 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-4 and IL-10 were determined by TaqMan single nucleotide polymorphism (SNP) genotyping assay. Odds ratio (OR) with 95% confidence intervals (CIs) was estimated by conditional logistic regression model.
  
  
  CONCLUSIONS
  A total of 89 incident ATDH cases and 356 controls undergoing antituberculosis treatment were included. Six SNPs were selected for genotyping, which were rs2243289, rs2243250 and rs2070874 for IL-4, and rs1800896, rs1800871 and rs1800872 for IL-10. No significant difference was observed in genotypes frequencies of the six selected SNPs between case and control group, and the distributions of IL-4 and IL-10 haplotypes were similar in ATDH patients and controls.
  
  
  CONCLUSIONS
  This study is the first attempt to evaluate the associations of genetic polymorphisms of IL-4 and IL-10 genes with ATDH using a nested case-control study design. We provide preliminary evidence that there is no statistically significant association between IL-4 and IL-10 genotypes/haplotypes and the risk of ATDH in Chinese population.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Tang
authors.forename: X
authors.initials: X
authors.lastname: Lv
authors.forename: S
authors.initials: S
authors.lastname: Wu
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Xia
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Zhan
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects*; D044466:Asian People; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000208:ethnology*; D002681:China / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies
chemical_list: D000995:Antitubercular Agents; D016753:Interleukin-10; D015847:Interleukin-4
keywords: IL-10; IL-4; antituberculosis treatment; drug-induced hepatotoxicity; nested case-control study