title: Interleukin 18 promoter variants (-137G>C and -607C>A) in patients with chronic hepatitis C: association with treatment response.
abstract: BACKGROUND
  Recently, two functional IL18 promoter variants, -607C>A (rs1946518) and -137G>C (rs187238), were associated with viral clearance in patients with hepatitis C. The present study focused on their relevance for treatment response.
  
  
  METHODS
  Seven hundred fifty-seven chronically infected European patients and 791 controls were enrolled in the study. IL18 genotyping was performed by allele-specific PCR. Liver histology was available in 67.9%.
  
  
  RESULTS
  Genotype and allele frequencies were equally distributed in patients and controls. No significant association with various disease characteristics was observed. However, when comparing patients with sustained virological response (SR) and non-SR, statistically significant associations were found for both variants (p = 0.0416 and p = 0.0274, respectively). In viral genotype 1, the -607A allele was positively associated with treatment response (p = 0.0190; OR 1.537; 95% CI, 1.072-2.205) and the -137G allele with a higher rate of nonresponse (p = 0.0302; OR 1.524; 95% CI, 1.040-2.233).
  
  
  CONCLUSIONS
  The association of IL18 variants with treatment response in genotype 1 hepatitis C patients implies a predictive and modifying role of these genetic variants.
authors.affiliation: Department of Medicine II, Medical Faculty at Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Stephan L
authors.initials: SL
authors.lastname: Haas
authors.forename: Christel
authors.initials: C
authors.lastname: Weiss
authors.forename: Peter
authors.initials: P
authors.lastname: Bugert
authors.forename: Jutta
authors.initials: J
authors.lastname: Gundt
authors.forename: Heiko
authors.initials: H
authors.lastname: Witt
authors.forename: Manfred V
authors.initials: MV
authors.lastname: Singer
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Ulrich
authors.initials: U
authors.lastname: Böcker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000276:immunology* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D020382:Interleukin-18 / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000276:immunology; D012367:RNA, Viral / Q000032:analysis; D012254:Ribavirin / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D016898:Interferon-alpha; D020382:Interleukin-18; D012367:RNA, Viral; D012254:Ribavirin