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

doi:10.1053/gast.2003.50061

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 journal › Article › peer-review

113 Scopus citations

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 language	English (US)
Pages (from-to)	352-360
Number of pages	9
Journal	Gastroenterology
Volume	124
Issue number	2
DOIs	https://doi.org/10.1053/gast.2003.50061
State	Published - Feb 1 2003
Externally published	Yes

ASJC Scopus subject areas

Gastroenterology

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10.1053/gast.2003.50061

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Promrat, K., McDermott, D. H., Gonzalez, C. M., Kleiner, D. E., Koziol, D. E., Lessie, M., Merrell, M., Soza, A., Heller, T., Ghany, M., Park, Y., Alter, H. J., Hoofnagle, J. H., Murphy, P. M., & Liang, T. J. (2003). Associations of chemokine system polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C. Gastroenterology, 124(2), 352-360. https://doi.org/10.1053/gast.2003.50061

Promrat, K, McDermott, DH, Gonzalez, CM, Kleiner, DE, Koziol, DE, Lessie, M, Merrell, M, Soza, A, Heller, T, Ghany, M, Park, Y, Alter, HJ, Hoofnagle, JH, Murphy, PM & Liang, TJ 2003, 'Associations of chemokine system polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C', Gastroenterology, vol. 124, no. 2, pp. 352-360. https://doi.org/10.1053/gast.2003.50061

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title = "Associations of chemokine system polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C",

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.",

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

year = "2003",

month = feb,

day = "1",

doi = "10.1053/gast.2003.50061",

language = "English (US)",

volume = "124",

pages = "352--360",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W.B. Saunders Ltd",

number = "2",

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TY - JOUR

T1 - Associations of chemokine system polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C

AU - Promrat, Kittichai

AU - McDermott, David H.

AU - Gonzalez, Carlos M.

AU - Kleiner, David E.

AU - Koziol, Deloris E.

AU - Lessie, Matthew

AU - Merrell, Maya

AU - Soza, Alejandro

AU - Heller, Theo

AU - Ghany, Marc

AU - Park, Yoon

AU - Alter, Harvey J.

AU - Hoofnagle, Jay H.

AU - Murphy, Philip M.

AU - Liang, T. Jake

PY - 2003/2/1

Y1 - 2003/2/1

N2 - 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.

AB - 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.

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

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