Genetic polymorphisms in non-alcoholic fatty liver disease: Interleukin-6−174G/C polymorphism is associated with non-alcoholic steatohepatitis

BackgroundEnvironmental and genetic factors play a role in the pathogenesis and natural history of non-alcoholic fatty liver disease (NAFLD).MethodsIn 114 subjects with NAFLD we report the prevalence and correlation with clinical parameters of three polymorphisms: interleukin-6 (−174G/C), plasma cell differentiation antigen (K121Q) and microsomal transfer protein (−493G/T).In 59 biopsied patients with NAFLD the polymorphisms were also related to histological features.ResultsIL-6 −174C variant was more prevalent (p < 0.01) in NAFLD compared to controls. In the NAFLD group, C carriers had higher HOMA-IR and fasting insulin than G carriers (p < 0.05). The prevalence of IL-6/C variant was higher (83%) in biopsied than in not biopsied subjects (66%) (p < 0.05). In biopsied subjects, C carriers had higher HOMA and fasting insulin (p < 0.05) compared than those with G allele. The prevalence of IL-6 −174G/C polymorphism was significantly higher in NASH than in NAFLD (p = 0.048). At logistic regression analysis IL-6 −174C was an independent predictor of both NAFLD (OR 4.116, C.I. 1.126–15.048) and NASH (OR 7.035, C.I. 1.167–42.394). Conversely, the distribution of PC-1 and MTP polymorphisms was not significantly different compared to the control group, nor associated with clinical or histological characteristics.ConclusionsOur data suggest that IL-6 −174C genetic polymorphisms, involved in inflammation and insulin resistance, are associated with NASH. These data may contribute to the understanding of the genetic susceptibility to NAFLD.