title: The Delta 32 mutation of the chemokine-receptor 5 gene neither is correlated with chronic hepatitis C nor does it predict response to therapy with interferon-alpha and ribavirin.
abstract: Unlike in HIV, homozygosity for a 32-bp deletion (Delta 32) of the chemokine receptor 5 (CCR5) gene was recently described in increased frequency in patients with chronic hepatitis C (HCV). Thus, it was speculated that this mutation might be relevant for disease susceptibility and influence the response to antiviral therapy. The present study sought to confirm the association between HCV and the Delta 32 mutation of the CCR5 gene and to correlate it with the response to therapy with interferon-alpha-2a and ribavirin. Sixty-two patients with HCV and 119 healthy unrelated controls were genotyped for the Delta 32 mutation. For the correlation between the Delta 32 mutation and response to therapy, only patients (n = 59) who completed 6 months of combination therapy as part of a prospective study were evaluated. The Delta 32 mutation was not observed in increased frequency in HCV. Furthermore, a significant difference of the HCV load or aminotransferase concentrations was not observed in carriers versus noncarriers of the Delta 32 mutation. After stratification for potentially confounding factors such as gender or HCV genotype, a significant difference was also not detected with respect to treatment outcome. These observations argue strongly against a role of CCR5 for susceptibility to HCV infection or response to combination therapy.
authors.affiliation: Medizinische Klinik, Klinikum der Ludwig-Maximilians Universität München, Standort Innenstadt, Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Glas
authors.forename: H P
authors.initials: HP
authors.lastname: Török
authors.forename: C
authors.initials: C
authors.lastname: Simperl
authors.forename: A
authors.initials: A
authors.lastname: König
authors.forename: K
authors.initials: K
authors.lastname: Martin
authors.forename: F
authors.initials: F
authors.lastname: Schmidt
authors.forename: M
authors.initials: M
authors.lastname: Schaefer
authors.forename: U
authors.initials: U
authors.lastname: Schiemann
authors.forename: C
authors.initials: C
authors.lastname: Folwaczny
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D009154:Mutation; D019713:Receptors, CCR5 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D012254:Ribavirin / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D019713:Receptors, CCR5; D012254:Ribavirin