title: Association between IL28B polymorphism, TNFα and biomarkers of insulin resistance in chronic hepatitis C-related insulin resistance.
abstract: TNFα 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 TNFα. The aim of this study was to investigate the relationship between IL28B rs12979860 genotype, the level of TNFα 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 TNFα (sTNFR1) 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 sTNFR1 (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 sTNFR1 and adipokines. Independent factors associated with IR were ferritin (OR = 1.002, P = 0.02), leptin (OR = 1.06, P = 0.02) and sTNFR1 (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 TNFα independent of IL28B genotype.
authors.affiliation: Service d'Hépatologie, APHP, Hôpital Saint-Antoine, Paris, France.|UPMC Université Paris 06, UMR_S938, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Lemoine
authors.affiliation: APHP, Laboratoire de Virologie, Hopital Henri Mondor, Créteil, France.|INSERM U955, Université Paris-Est Créteil, Créteil, France.
authors.forename: S
authors.initials: S
authors.lastname: Chevaliez
authors.affiliation: UPMC Université Paris 06, UMR_S938, Paris, France.|Service de biochimie et hormonologie, APHP, Hôpital Tenon, Paris, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Bastard
authors.affiliation: Service d'Hépatologie, APHP, Hôpital Saint-Antoine, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Fartoux
authors.affiliation: Service d'Hépatologie, APHP, Hôpital Saint-Antoine, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Chazouillères
authors.affiliation: UPMC Université Paris 06, UMR_S938, Paris, France.|Service de biochimie et hormonologie, APHP, Hôpital Tenon, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Capeau
authors.affiliation: APHP, Laboratoire de Virologie, Hopital Henri Mondor, Créteil, France.|INSERM U955, Université Paris-Est Créteil, Créteil, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Pawlotsky
authors.affiliation: Service d'Hépatologie, APHP, Hôpital Saint-Antoine, Paris, France.|UPMC Université Paris 06, UMR_S938, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Serfaty
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000473:pathology; D006801:Humans; D007333:Insulin Resistance; D007372:Interferons; D015850:Interleukin-6 / Q000097:blood; D007378:Interleukins / Q000235:genetics*; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D007372:Interferons; D015850:Interleukin-6; D007378:Interleukins; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: IL28B; chronic hepatitis C; hepatitis C virus; insulin resistance; leptin, adiponectin; tumour necrosis factor alpha