Interleukin-4 and interleukin-10 polymorphisms and antituberculosis drug-induced hepatotoxicity in Chinese population

What is known and 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.

Results and discussion: 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.

What is new and conclusion: 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.