Analysis of IL-6, STAT3 and HSPA1L Gene Polymorphisms in Anti-Tuberculosis Drug-Induced Hepatitis in a Nested Case-Control Study

OBJECTIVES: 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). CONCLUSION: 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.