CCR5 haplotypes influence HCV serostatus in Caucasian intravenous drug users.
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.
Department of Microbiology, Faculty of Medicine, University of Tartu, Tartu, Estonia.
Kristi
K
Huik
Radko
R
Avi
Andrew
A
Carrillo
Nathan
N
Harper
Merit
M
Pauskar
Maarja
M
Sadam
Tõnis
T
Karki
Tõnu
T
Krispin
Ulvi-Kaire
UK
Kongo
Tatiana
T
Jermilova
Kristi
K
Rüütel
Ave
A
Talu
Katri
K
Abel-Ollo
Anneli
A
Uusküla
Sunil K
SK
Ahuja
Weijing
W
He
Irja
I
Lutsar
D000328:Adult; D019742:Chemokines, CC / Q000097:blood / Q000235:genetics / Q000276:immunology; D060085:Coinfection; D004957:Estonia / Q000453:epidemiology; D005260:Female; D015870:Gene Expression; D006679:HIV Seropositivity / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006239:Haplotypes; D016174:Hepacivirus / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006801:Humans; D008297:Male; D015995:Prevalence; D019713:Receptors, CCR5 / Q000097:blood / Q000235:genetics* / Q000276:immunology; D015819:Substance Abuse, Intravenous / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000821:virology; D044465:White People
C492767:CCL3L1 protein, human; C584933:CCR5 protein, human; D019742:Chemokines, CC; D019713:Receptors, CCR5