title: IL-10 and IL-28B gene variants as predictors of sustained response to peginterferon and ribavirin therapy in chronic HCV infection.
abstract: Interleukin-10 (IL-10) plays an important role in the immunity to hepatitis C virus (HCV). Insofar as IL-10 variants are associated with altered levels of IL-10, previous studies that examined the association of IL-10 polymorphisms with the susceptibility to and progression of chronic HCV, and response to anti-viral treatment were inconsistent. We investigated the association between common IL-10 variants in the intron and the promotor region with HCV and associated features.
  
  
  
  Study subjects comprised 120 patients infected with HCV-1b, and treated with Peg-IFN/RBV. Genotyping of six IL-10 promoter variants in the intron region (rs1878672, rs1554286, rs1518111) and promotor region (rs1800872, rs1800871, rs1800896) were done by real-time PCR.
  
  
  
  Compared to G/G, carriage of IL-10 rs1800896 (-1082A/G) A/A genotype was more frequent in patients with sustained virological response (SVR). The decline in viral load over the first 12weeks of treatment was more pronounced in rs1800896 A/A genotype carriers, compared to G/G genotype carriers, and was irrespective of the treatment dosage. Carriage of rs1800896 A/A genotype was positively associated with improvement in viral load decline, which was simultaneous, with and without carriage of the common favourable IL-28B variant. Carriage of both IL-10 rs1800896 G/G and IL-28B non-favourable genotype was associated with twice the risk of getting slow decline of viral load during treatment. Haploview analysis identified ACGCTA and CCGCTG haplotypes to be linked with excellent PegIFN/RBV cure rate, and complete HCV eradication. On the other hand, ACGCTG and CCGCTA haplotypes were associated with resistance to PegIFN/RBV treatment.
  
  
  
  IL-10 rs1800896 variant markedly influences the clinical outcome of HCV infection, and is a determinant of the response to HCV treatment.
authors.affiliation: University of Tunis El Manar, Faculty of Sciences of Tunis, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, 2092, Tunisia. Electronic address: sghaiere.ikram@gmail.com.
authors.forename: Ikram
authors.initials: I
authors.lastname: Sghaier
authors.affiliation: Charles Nicolle Hospital, Hepato-Gastro-Enterology Department, Tunis, Tunisia.
authors.forename: Leila
authors.initials: L
authors.lastname: Mouelhi
authors.affiliation: Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain.
authors.forename: Noor A
authors.initials: NA
authors.lastname: Rabia
authors.affiliation: Military Hospital of Tunis, Laboratory of Immunology, Tunis, Tunisia.
authors.forename: Ezzedine
authors.initials: E
authors.lastname: Ghazoueni
authors.affiliation: Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain.
authors.forename: Wassim Y
authors.initials: WY
authors.lastname: Almawi
authors.affiliation: University of Tunis El Manar, Faculty of Sciences of Tunis, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, 2092, Tunisia.
authors.forename: Besma Yacoubi
authors.initials: BY
authors.lastname: Loueslati
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D007372:Interferons / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D007378:Interleukins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D007378:Interleukins; D016753:Interleukin-10; D012254:Ribavirin; D007372:Interferons
keywords: HCV; IL-10; IL-28B; Polymorphisms