Associations of chemokine system polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C

Kittichai Promrat, David H. McDermott, Carlos M. Gonzalez, David E. Kleiner, Deloris E. Koziol, Matthew Lessie, Maya Merrell, Alejandro Soza, Theo Heller, Marc Ghany, Yoon Park, Harvey J. Alter, Jay H. Hoofnagle, Philip M. Murphy, T. Jake Liang

Research output: Contribution to journalArticlepeer-review

Abstract

Background & Aims: CCR5Δ32, a 32-base pair deletion of the CC chemokine receptor (CCR) 5 gene, is associated with slowed human immunodeficiency virus disease progression in heterozygotes and protection against infection in homozygotes. A recent study found a higher than expected frequency of CCR5Δ32/Δ32 in patients with hepatitis C virus infection. The roles of other disease-associated chemokine system polymorphisms have not been evaluated in hepatitis C virus infection. Methods: Six chemokine system polymorphisms (CCR5Δ32, CCR5 promoter 59029-G/A, CCR2 -64I, RANTES [regulated upon activation, normal T cells expressed and secreted] -403 -G/A, and -28 -C/G and stromal derived factor 1 -3′A) were studied in 417 patients with liver diseases (339 with hepatitis C) and 2380 blood donors. The clinical parameters of hepatitis C virus infection were compared between carriers and noncarriers of each genetic variant. Results: The frequency of CCR5Δ32 homozygosity was 0.8% in whites with hepatitis C virus and 1.1% in controls (P = 0.75). The CCR5Δ32 allele was not associated With any of the clinical parameters of hepatitis C virus infection. Hepatitis C virus-seropositive whites with the RANTES -403 -A allele were less likely to have severe hepatic inflammation compared with those without (Odds ratio, 0.34; P = 0.03). In multivariate analysis, the CCR5 promoter 59029 -A allele was marginally associated with a sustained response to interferon therapy (odds ratio, 3.07; P = 0.048). Conclusions: In this cohort, the frequency of CCR5Δ32 homozygosity in patients with hepatitis C was similar to controls. The high prevalence of CCR5Δ32 homozygosity in the hepatitis C virus patients of the erlier study likely reflects resistance to human immunodeficiency virus infection in hemophiliacs rather than a susceptibility to hepatitis C virus infection. Expression of CCR5 and RANTES may be important in the modulation of hepatic inflammation and response to interferon therapy in chronic hepatitis C.

Original languageEnglish (US)
Pages (from-to)352-360
Number of pages9
JournalGastroenterology
Volume124
Issue number2
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Gastroenterology

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