BACKGROUND & AIMS: CCR5Delta32, 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 CCR5Delta32/Delta32 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 (CCR5Delta32, 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 CCR5Delta32 homozygosity was 0.8% in whites with hepatitis C virus and 1.1% in controls (P = 0.75). The CCR5Delta32 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 CCR5Delta32 homozygosity in patients with hepatitis C was similar to controls. The high prevalence of CCR5Delta32 homozygosity in the hepatitis C virus patients of the earlier 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.
BACKGROUND & AIMS:CCR5Delta32, 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 CCR5Delta32/Delta32 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 (CCR5Delta32, 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 CCR5Delta32 homozygosity was 0.8% in whites with hepatitis C virus and 1.1% in controls (P = 0.75). The CCR5Delta32 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 CCR5Delta32 homozygosity in patients with hepatitis C was similar to controls. The high prevalence of CCR5Delta32 homozygosity in the hepatitis C viruspatients of the earlier 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.
Authors: Karl S Lang; Panco Georgiev; Mike Recher; Alexander A Navarini; Andreas Bergthaler; Mathias Heikenwalder; Nicola L Harris; Tobias Junt; Bernhard Odermatt; Pierre-Alain Clavien; Hanspeter Pircher; Shizuo Akira; Hans Hengartner; Rolf M Zinkernagel Journal: J Clin Invest Date: 2006-09 Impact factor: 14.808
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Authors: Rosa Zampino; Aldo Marrone; Luciano Restivo; Barbara Guerrera; Ausilia Sellitto; Luca Rinaldi; Ciro Romano; Luigi E Adinolfi Journal: World J Hepatol Date: 2013-10-27
Authors: Ankur Goyal; P V Suneetha; G T Kumar; Deepak K Shukla; Naveen Arora; Shiv K Sarin Journal: World J Gastroenterol Date: 2006-08-07 Impact factor: 5.742
Authors: Ekihiro Seki; Samuele De Minicis; Geum-Youn Gwak; Johannes Kluwe; Sayaka Inokuchi; Christina A Bursill; Josep M Llovet; David A Brenner; Robert F Schwabe Journal: J Clin Invest Date: 2009-07 Impact factor: 14.808
Authors: Hermann E Wasmuth; Alexa Werth; Tobias Mueller; Thomas Berg; Christoph G Dietrich; Andreas Geier; Ramin Schirin-Sokhan; Carsten Gartung; Johann Lorenzen; Siegfried Matern; Frank Lammert Journal: J Mol Med (Berl) Date: 2003-12-13 Impact factor: 4.599