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C-C chemokine receptor 2 and C-C chemokine receptor 5 genotypes in patients treated for chronic hepatitis C virus infection

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Abstract

We explored the influence of the major CCR5 promoter or coding region variants as haplotypes and genotypes in a cohort of 250 chronically infected HCV patients receiving combined interferon/ribavirin therapy. No haplotype, including the D32-bearing haplotype (G*2) reportedly associated in homozygotes with high HCV viral load (VL), showed a similar effect. Patients with genotype C/G*2 showed slightly lower median VL (p=0.05). Neither the G*2 haplotype nor the C/G*2 genotype influenced viral dynamics during the initial 12 wk of treatment (p=0.53). The genotype E/E was more frequent among sustained responders (15.5%) than non-responders (7.8%), and VL declined further among E/E homozygotes during the initial 12 wk of treatment, particularly those with HCV genotype 1 (p=0.016). Differential receptor expression due to E/E homozygosity in HCV infection remains to be confirmed.

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References

  1. McNicholl JM, Downer MV, Udhayakumar V, Alper CA, Swerdlow DL: Host-pathogen interactions in emerging and reemerging infectious diseases: a genomic perspective of tuberculosis, malaria, human immunodeficiency virus infection, hepatitis B, and cholera. Annu Rev Public Health 2000;21:15–46.

    Article  PubMed  CAS  Google Scholar 

  2. Cooke GS, Hill AV: Genetics of susceptibility to human infectious disease. Nat Rev Genet 2001;2: 967–977.

    Article  PubMed  CAS  Google Scholar 

  3. Kaslow RA, McNicholl JM: Genetic determinants of HIV-1 infection and its manifestations. Proc Assoc Am Physicians 1999; 111:299–307.

    Article  PubMed  CAS  Google Scholar 

  4. Carrington M, Nelson GW, Martin MP, et al: HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage Science 1999;283:1748–1752.

    Article  PubMed  CAS  Google Scholar 

  5. Tang J, Shelton B, Makhatadze NJ, et al: Distribution of chemokine receptor CCR2 and CCR5 genotypes and their relative contribution to human immunodeficiency virus type 1 (HIV-1) seroconversion, early HIV-1 RNA concentration in plasma, and later disease progression. J Virol 2002;76: 662–672.

    Article  PubMed  CAS  Google Scholar 

  6. Thursz MR: Host genetic factors influencing the outcome of hepatitis. J Viral Hepat 1997;4:215–220.

    Article  PubMed  CAS  Google Scholar 

  7. Powell EE, Edwards-Smith CJ, Hay JL, et al: Host genetic factors influence disease progression in chronic hepatitis C. Hepatology 2000;31:828–833.

    Article  PubMed  CAS  Google Scholar 

  8. Thio CL, Thomas DL, Carrington M: Chronic viral hepatitis and the human genome. Hepatolgogy 2000;31:819–827.

    Article  CAS  Google Scholar 

  9. Thursz M. Genetic susceptibility in chronic viral hepatitis. Antiviral Res 2001;52:113–116.

    Article  PubMed  CAS  Google Scholar 

  10. Thomas DL, Astemborski J, Rai RM, et al: The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA 2000;284:450–456.

    Article  PubMed  CAS  Google Scholar 

  11. Lauer GM, Walker BD: Hepatitis C virus infection. N Engl J Med 2001;345:41–52.

    Article  PubMed  CAS  Google Scholar 

  12. Villano SA, Vlahov D, Nelson KE, Cohn S, Thomas DL: Persistence of viremia and the importance of long-term follow-up after acute hepatitis C infection. Hepatology 1999;29:908–914.

    Article  PubMed  CAS  Google Scholar 

  13. Edwards-Smith CJ, Jonsson JR, Purdie DM, Bansal A, Shorthouse C, Powell EE: Interleukin-10 promoter polymorphism predicts initial response of chronichepatitis C to interferon alfa. Hepatology 1999;30:526–530.

    Article  PubMed  CAS  Google Scholar 

  14. Knolle PA, Kremp S, Hohler T, Krummenauer F, Schirmacher P, Gerken G: Viral and host factors in the prediction of response to interferon-alpha the rapy in chronic hepatitis C after long-term follow-up. J Viral Hepat 1998;5:399–406.

    Article  PubMed  CAS  Google Scholar 

  15. Thio CL, Carrington M, Marti D, et al: Class II HLA alleles and hepatitis B virus persistence in African Americans. J Infect Dis 1999;179:1004–1006.

    Article  PubMed  CAS  Google Scholar 

  16. Thursz M, Yallop R, Goldin R, Trepo C, Thomas HC: Influence of MHC class II genotypeonoutcome of infection with hepatitis C virus. The HENCORE group. Hepatitis C European Network for Cooperative Research. Lancet 1999;354: 2119–2124.

    Article  PubMed  CAS  Google Scholar 

  17. Harcourt G, Hellier S, Bunce M, et al: Effect of HLA class II genotype on T helper lymphocyte responses and viral control in hepatitis C virus infection. J Viral Hepat 2001;8:174–179.

    Article  PubMed  CAS  Google Scholar 

  18. Yee LJ, Tang J, Herrera J, Kaslow RA, van Leeuwen DJ: Tumor necrosis factor gene polymorphisms in patients with cirrhosis from chronic hepatitis C virus infection. Genes Immun 2000;1: 386–390.

    Article  PubMed  CAS  Google Scholar 

  19. Yee LJ, Tang J, Gibson AW, Kimberly R, Van Leeuwen DJ, Kaslow RA: Interleukin 10 polymorphisms as predictors of sustained response in antiviral therapy for chronic hepatitis C infection. Hepatology 2001;33:708–712.

    Article  PubMed  CAS  Google Scholar 

  20. Woitas RP, Ahlenstiel G, Brackmann HH, Matz B, Rockstroh JK, Spengler U: CCR5-D32 mutation—protective against HIV, but bad for hepatitis C virus? 8th Conference on Retroviruses and Opportunistic Infections, 2000:192–193, #19 (abstract no. 499).

    Google Scholar 

  21. Woitas RP, Ahlenstiel G, Rockstroh JK, et al: Increased frequency of the CC-chemokine receptor 5-D32/D32 genotype in hepatitis C. J Hepatol 2001;34(Suppl. 1): 164 (abstract no. 1071).

    Google Scholar 

  22. Woitas RP, Ahlenstiel G, Iwan A, et al: Frequency analysis of the HIV-protective CC chemokine receptor 2B V641 mutation in patients with Hepatitis C and HIV/HCV coinfection. Hepatology 2001;34:480A (abstract no. 1231).

    Google Scholar 

  23. Yoshie O, Imai T, Nomiyama H: Chemokines in immunity. Adv Immunol 2001;78:57–110.

    Article  PubMed  CAS  Google Scholar 

  24. Tang J, Rivers C, Karita E, et al: Allelic variants of human beta-chemokine receptor 5 (CCR5) promoter: evolutionary relationships and predictable association with HIV-1 disease progression. Genes Immun 1999;1:20–27.

    Article  PubMed  CAS  Google Scholar 

  25. McHutchison JG, Gordon SC, Schiff ER, et al: Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med 1998;339:1485–1492.

    Article  PubMed  CAS  Google Scholar 

  26. Poynard T, Marcellin P, Lee SS, et al: Randomised trial of interferon alpha 2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha 2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet 1998;352: 1426–1432.

    Article  PubMed  CAS  Google Scholar 

  27. Yee LJ, Weiss HL, Langner RG, Herrera J, Kaslow RA, van Leeuwen DJ: Risk factors for acquisition of hepatitis C virus infection: a case series and potential implications for disease surveillance. BMC Infect Dis 2001;1:8.

    Article  PubMed  CAS  Google Scholar 

  28. Gonzalez E, Bamshad M, Sato N, et al: Race-specific HIV-1 disease modifying effects associated with CCR5 haplotypes. Proc Natl Acad Sci USA 1999;96:12,004–12,009.

    CAS  Google Scholar 

  29. Mangano A, Gonzalez E, Dhanda R, et al: Concordance between the CC chemokine receptor 5 genetic determinants thatalter risks of transmission and disease progression in children exposed perinatally to human immunodeficiency virus. J Infect Dis 2001;183:1574–1585.

    Article  PubMed  CAS  Google Scholar 

  30. Howard OM, Shirakawa AK, Turpin JA, et al: Naturally occurring CCR5 extracellular and transmembrane domain variants affect HIV-1 co-receptorandligand binding function. J Biol Chem 1999; 274:16,228–16,234.

    CAS  Google Scholar 

  31. Alric L, Izopet J, Fort M, et al: Study of the association between major histocompatibility complex class II genes and the response to interferon alpha in patients with chronic hepatitis C infection. Hum Immunol 1999;60:516–523.

    Article  PubMed  CAS  Google Scholar 

  32. Neumann AU, Lam NP, Dahari H, et al: Differences in viral dynamics between genotypes 1 and 2 of hepatitis C virus. J Infect Dis 2000;182:28–35.

    Article  PubMed  CAS  Google Scholar 

  33. Zein NN: Clinical significance of hepatitis C virus genotypes. Clin Microbiol Rev 2000;13:223–235.

    Article  PubMed  CAS  Google Scholar 

  34. Alric L, Fort M, Izopet J, et al: Study of host- and virus-related factors associated with spontaneous hepatitis C virus clearance. Tissue Antigens 2000;56:154–158.

    Article  PubMed  CAS  Google Scholar 

  35. Dean M, Carrington M, Winkler C, et al: Genetic restriction of HIV-1 infection and progression to AIDS by a common deletion allele of the chemokine receptor 5 structural gene. Science 1996;273: 1856–1862.

    Article  PubMed  CAS  Google Scholar 

  36. Lu Y, Nerurkar VR, Dashwood WM, et al: Genotype andallele frequency of a 32-base pair deletion mutation in the CCR5 gene in various ethnic groups: absence of mutation among Asians and Pacific Islanders. Int J Infect Dis 1999;3: 186–191.

    Article  PubMed  CAS  Google Scholar 

  37. Libert F, Cochaux P, Beckman G, et al: The deltaccr5 mutation conferring protection against HIV-1 in Caucasian populations has a single and recent origin in Northeastern Europe. Hum Mol Genet 1998;7: 399–406.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Epidemiology and International Health, School of Public Health, University of Alabama at Birmingham, 35294-0022, Birmingham, AI

    M. Tevfik Dorak, Gbolahan O. Folayan, Leland J. Yee, Jianning Tang &  Richard A. Kaslow

  2. Comprehensive Cancer Center, Biostatistics Unit, University of Alabama at Birmingham, 35294-0022, Birmingham, AI

    Santosh Niwas

  3. Division of Gastroenterology/Hepatology (UAB Liver Center), University of Alabama at Birmingham, 35294-0022, Birmingham, AI

    Dirk J. van Leeuwen

Authors
  1. M. Tevfik Dorak
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  2. Gbolahan O. Folayan
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  3. Santosh Niwas
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  4. Dirk J. van Leeuwen
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  5. Leland J. Yee
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  6. Jianning Tang
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  7. Richard A. Kaslow
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Correspondence to Richard A. Kaslow.

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Dorak, M.T., Folayan, G.O., Niwas, S. et al. C-C chemokine receptor 2 and C-C chemokine receptor 5 genotypes in patients treated for chronic hepatitis C virus infection. Immunol Res 26, 167–175 (2002). https://doi.org/10.1385/IR:26:1-3:167

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  • DOI: https://doi.org/10.1385/IR:26:1-3:167

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