The Role of Interleukin-6 and Interleukin-8 Gene Polymorphisms in Non-Alcoholic Steatohepatitis

BACKGROUND Genetic polymorphisms may play role in the pathophysiology of nonalcoholic steatohepatitis (NASH). OBJECTIVES We purposed to assess the role of interleukin 6 (IL 6) and interleukin 8 (IL 8) gene polymorphisms in the pathogenesis of NASH. PATIENTS AND METHODS Consecutive patients with biopsy proven NASH and age- and gender-matched healthy individuals with normal liver function tests and normal ultrasonography were enrolled in the study. Histopathological findings were recorded according to nonalcoholic fatty liver disease activity score (NAS). Patients were classified according to fibrosis scores as fibrosis score < 2 (mild fibrosis group) and fibrosis score ≥ 2 (significant fibrosis group). Blood samples were collected and genomic DNA isolation kit was used to evaluate genetic polymorphisms. RESULTS Of thirty-eight patients, 27 (71%) were in mild fibrosis group and 11 (29%) in significant fibrosis group. Thirty-eight age- and gender-matched healthy controls were enrolled in the study. The frequencies of genotypes G/C and G/G of IL 6 among the NASH group and healthy controls were 39.5% and 60.5% vs. 53.6% and 46.4%, respectively (P = 0.32). The frequencies of the genotypes of IL 8 among the NASH group were 47.2%, 44.6%, and 8.2% for T/T, A/T, and A/A, and in healthy controls were 50%, 28.6% and 21.4%, respectively, (P = 0.568). The differences between IL 8 gene T/A and T/T genotypes were not significant statistically (P > 0.05). However, the frequency of A/A genotype in significant fibrosis group was higher than the mild fibrosis group (P = 0.0016). The differences of -251 A/T polymorphism in the IL 8 and -174 C/G polymorphism in the IL 6 were not statistically significant between fibrosis groups (P > 0.05). CONCLUSIONS IL6 and IL8 gene polymorphisms have no role in NASH pathogenesis and liver fibrosis process, but presence of the A/A genotype in the IL8 gene is associated with disease progression.