title: Genetic polymorphisms of ICAM 1 and IL28 as predictors of liver fibrosis severity and viral clearance in hepatitis C genotype 4.
abstract: OBJECTIVE
  Intercellular adhesion molecule-1 (ICAM-1) is located on chromosome 19p13.2, and this protein plays an important role in the pathogenesis of the hepatitis C virus (HCV). The rs12979860 polymorphism of the IL-28B gene participates in HCV clearance. This study investigated the association of the genetic markers (SNPs), rs5496, rs281437 and rs12979860 polymorphisms, with viral clearance and the progression of hepatic fibrosis in HCV genotype 4 patients who were treated with pegylated interferon and ribavirin.
  
  
  METHODS
  Thirty consecutive HCV genotype 4 patients who were treated with pegylated interferon and ribavirin therapy for 48 weeks were grouped into responders (control group) and non-responders (case group). The severity of fibrosis was classified according to the Scheuer Score. SNP genotyping of rs5496 [A/G], rs281437 [C/T] and rs12979860 [C/T] were performed using the 5' nuclease assay with a TaqMan MGB probe in an ABI 7500 Fast Real-Time PCR System (Applied Biosystems).
  
  
  RESULTS
  All SNPs exhibited Hardy-Weinberg Equilibrium (HWE). The patients with the C allele of rs12979860 exhibited an approximately eight times higher risk of SVR compared to patients with the T allele (aOR=7.98; CI: 1.07-59.36, P=0.012). No significant association of rs5496 and rs281437 with treatment response was detected (P=0.185 and P=0.123, respectively). Patients with the T allele of rs281437 exhibited an approximately 13 times higher risk of severe fibrosis compared to patients with the C allele (aOR=13.0; CI: 1.32-128.11, P= 0.028). No significant association of the other genetic variants with the degree of fibrosis in the study subjects was detected for rs5496 and rs12979860.
  
  
  CONCLUSIONS
  The present study revealed associations between the ICAM-1 gene marker, rs281437, and the progression of hepatic fibrosis in HCV genotype 4 and rs12979860 of the IL-28 B gene with viral clearance.
authors.affiliation: Health Sciences Department, Qatar University, 2713 Doha, Qatar.
authors.forename: Nasser M
authors.initials: NM
authors.lastname: Rizk
authors.forename: Moutaz F
authors.initials: MF
authors.lastname: Derbala
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000145:classification / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D012720:Severity of Illness Index; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D005819:Genetic Markers; D018799:Intercellular Adhesion Molecule-1; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a