title: The predictive value of IL28B gene polymorphism for spontaneous clearance in a single source outbreak cohort is limited in patients carrying the CCR5Δ32 mutation.
abstract: OBJECTIVE
  The CCR5Δ32 mutation has been suspected to adversely affect outcomes of HCV infection, although reports have remained controversial. Here, we investigated the relative genetic contributions of the CCR5Δ32 deletion and the IL28B rs12979860 polymorphisms to spontaneous clearance of hepatitis C in a single-source outbreak.
  
  
  METHODS
  We retrieved 396 Caucasian women (119 women with spontaneous HCV clearance) who had been infected with HCV genotype 1-contaminated anti-D immunoglobulin in 1978, and determined their IL28B and CCR5 alleles.
  
  
  RESULTS
  IL28B CC, CT, and TT genotypes were found in 35.4%, 50%, and 14.6% of patients and corresponded to spontaneous clearance rates of 50%, 21.2%, and 12.1% (Chi(2)=38.7, p=5.0×10(-10)), respectively. CCR5 WT/WT, WT/Δ32, and Δ32/Δ32 genotypes were observed in 76%, 22.7%, and 1.3% of patients and corresponded to clearance rates of 33.2%, 21.2%, and 0% (Chi(2)=6.9, p=0.009), respectively. In a stepwise forward-conditional multivariate regression model both CCR5 (OR 2.1, p=0.01 for WT/WT) and IL28B genetic variants (OR 4.3, p=4.6×10(-10) for the C/C genotype) were identified as independent predictors of spontaneous HCV clearance. Importantly, favorable response rates were associated with the IL28B CC genotype only in CCR5 wild-type homozygous women, while HCV clearance in CCR5Δ32 carriers remained poor even in patients with the rs12979860 CC genotype.
  
  
  CONCLUSIONS
  Both IL28B rs1297860 and CCR5Δ32 allelic variants are independent genetic determinants of spontaneous HCV clearance. The variable relative distribution between IL28B rs1297860 and CCR5Δ32 allelic variants in different populations may have masked the role of the CCR5Δ32 mutation in some studies.
authors.affiliation: Department of Internal Medicine, University of Bonn, Bonn, Germany. jacob.nattermann@ukb.uni-bonn.de
authors.forename: Jacob
authors.initials: J
authors.lastname: Nattermann
authors.forename: Jörg
authors.initials: J
authors.lastname: Timm
authors.forename: Hans Dieter
authors.initials: HD
authors.lastname: Nischalke
authors.forename: Anne
authors.initials: A
authors.lastname: Olbrich
authors.forename: Monika
authors.initials: M
authors.lastname: Michalk
authors.forename: Hans L
authors.initials: HL
authors.lastname: Tillmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.forename: Hannelore
authors.initials: H
authors.lastname: Tenckhoff
authors.forename: Manfred
authors.initials: M
authors.lastname: Wiese
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kullig
authors.forename: Uwe
authors.initials: U
authors.lastname: Göbel
authors.forename: Emanuela
authors.initials: E
authors.lastname: Capka
authors.forename: Ingolf
authors.initials: I
authors.lastname: Schiefke
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Güthof
authors.forename: Kurt
authors.initials: K
authors.lastname: Grüngreiff
authors.forename: Ingrid
authors.initials: I
authors.lastname: König
authors.forename: Michael
authors.initials: M
authors.lastname: Roggendorf
authors.forename: Tilman
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D004196:Disease Outbreaks; D004340:Drug Contamination; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006526:Hepatitis C / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000635:transmission / Q000821:virology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019713:Receptors, CCR5 / Q000235:genetics*; D017384:Sequence Deletion; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; D019713:Receptors, CCR5; C000624353:interferon-lambda, human; D000095022:Interferon Lambda