Association between IL 28B polymorphism, TNF α and biomarkers of insulin resistance in chronic hepatitis C‐related insulin resistance

Summary TNF α has been shown to play a role in hepatitis C virus ( HCV )‐induced insulin resistance ( IR ). Polymorphism of the IL 28B gene that encodes IFN ‐lambda 3 may be associated with IR through modulation of TNF α . The aim of this study was to investigate the relationship between IL 28B rs12979860 genotype, the level of TNF α activation and the degree of IR in patients with chronic hepatitis C. One hundred and thirty‐three nondiabetic genotype 1 HCV ‐infected patients with biopsy proven noncirrhotic hepatitis C were investigated for IR (using HOMA index), IL 28B rs12979860 genotype and fasting circulating levels of soluble receptor 1 of TNF α (s TNFR 1) and adipokines: leptin, adiponectin and IL ‐6. The HOMA ‐ IR was positively correlated with serum levels of leptin ( r  = 0.35, P  < 0.0001) and s TNFR 1 ( r  = 0.35, P  < 0.0001) but not with IL ‐6 or adiponectin. IL 28B rs12979860 CC genotype was observed in 35% patients. Genotype CC and nongenotype CC patients were similar in terms of HOMA ‐ IR (means 1.6 ± 0.9 vs 1.7 ± 1.4) and had similar circulating levels of s TNFR 1 and adipokines. Independent factors associated with IR were ferritin ( OR  = 1.002, P  = 0.02), leptin ( OR  = 1.06, P  = 0.02) and s TNFR 1 ( OR  = 7.9, P  = 0.04). This study suggests that in nondiabetic, noncirrhotic, HCV genotype 1‐infected patients, there is no relationship between IL 28B rs12979860 genotype and HOMA ‐ IR or sTNFR 1 level. HCV ‐related IR may be mediated through TNF α independent of IL 28B genotype.