CCR5 haplotypes influence HCV serostatus in Caucasian intravenous drug users

PLoS One. 2013 Jul 25;8(7):e70561. doi: 10.1371/journal.pone.0070561. Print 2013.

Abstract

Background: Up to 90% HIV-1 positive intravenous drug users (IDUs) are co-infected with HCV. Although best recognized for its function as a major co-receptor for cell entry of HIV, CC chemokine receptor 5 (CCR5) has also been implicated in the pathogenesis of HCV infection. Here, we investigated whether CCR5 haplotypes influence HIV-1 and HCV seropositivity among 373 Caucasian IDUs from Estonia.

Methods: Of these IDUs, 56% and 44% were HIV and HCV seropositive, respectively, and 47% were coinfected. 500 blood donors seronegative for HIV and HCV were also evaluated. CCR5 haplotypes (HHA to HHG*2) were derived after genotyping nine CCR2-CCR5 polymorphisms. The association between CCR5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis. Co-variates included in the models were length of intravenous drug use, HBV serostatus and copy number of CCL3L1, the gene encoding the most potent HIV-suppressive chemokine and ligand for CCR5.

Results: Compared to IDUs seronegative for both HCV and HIV (HCV-/HIV-), IDUs who were HCV+/HIV- and HCV+/HIV+were 92% and 82%, respectively, less likely to possess the CCR5-HHG*1 haplotype, after controlling for co-variates (P(adjusted) = 1.89 × 10(-4) and 0.003, respectively). This association was mostly due to subjects bearing the CCR5 HHE and HHG*1 haplotype pairs. Approximately 25% and<10% of HCV-/HIV- IDUs and HCV-/HIV- blood donors, respectively, possessed the HHE/HHG*1 genotype.

Conclusions: Our findings suggest that HHG*1-bearing CCR5 genotypes influence HCV seropositivity in a group of Caucasian IDUs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Chemokines, CC / blood
  • Chemokines, CC / genetics
  • Chemokines, CC / immunology
  • Coinfection
  • Estonia / epidemiology
  • European Continental Ancestry Group
  • Female
  • Gene Expression
  • HIV Seropositivity / epidemiology
  • HIV Seropositivity / ethnology
  • HIV Seropositivity / genetics*
  • HIV Seropositivity / virology
  • HIV-1 / isolation & purification*
  • Haplotypes
  • Hepacivirus / isolation & purification*
  • Hepatitis C, Chronic / ethnology
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / virology
  • Humans
  • Male
  • Prevalence
  • Receptors, CCR5 / blood
  • Receptors, CCR5 / genetics*
  • Receptors, CCR5 / immunology
  • Substance Abuse, Intravenous / ethnology
  • Substance Abuse, Intravenous / genetics*
  • Substance Abuse, Intravenous / immunology
  • Substance Abuse, Intravenous / virology

Substances

  • CCL3L1 protein, human
  • CCR5 protein, human
  • Chemokines, CC
  • Receptors, CCR5