CCR5 Haplotypes Influence HCV Serostatus in Caucasian Intravenous Drug Users

Kristi Huik, Radko Avi, Andrew Carrillo, Nathan Harper, Merit Pauskar, Maarja Sadam, Tõnis Karki, Tõnu Krispin, Ulvi Kaire Kongo, Tatiana Jermilova, Kristi Rüütel, Ave Talu, Katri Abel-Ollo, Anneli Uusküla, Sunil K. Ahuja, Weijing He, Irja Lutsar

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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 (Padjusted = 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.

Original languageEnglish (US)
Article numbere70561
JournalPloS one
Volume8
Issue number7
DOIs
StatePublished - Jul 25 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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