Association between IL28B polymorphism, TNF α and biomarkers of insulin resistance in chronic hepatitis C-related insulin resistance.

TNF α has been shown to play a role in hepatitis C virus ( HCV)-induced insulin resistance ( IR). Polymorphism of the IL28B 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 IL28B 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), IL28B rs12979860 genotype and fasting circulating levels of soluble receptor 1 of TNF α (s TNFR1) 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 TNFR1 ( r = 0.35, P < 0.0001) but not with IL-6 or adiponectin. IL28B 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 TNFR1 and adipokines. Independent factors associated with IR were ferritin ( OR = 1.002, P = 0.02), leptin ( OR = 1.06, P = 0.02) and s TNFR1 ( OR = 7.9, P = 0.04). This study suggests that in nondiabetic, noncirrhotic, HCV genotype 1-infected patients, there is no relationship between IL28B rs12979860 genotype and HOMA- IR or sTNFR1 level. HCV-related IR may be mediated through TNF α independent of IL28B genotype. [ABSTRACT FROM AUTHOR]