PloS one · 2013
CCR5 haplotypes influence HCV serostatus in Caucasian intravenous drug users.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПоддержка правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Huik Kristi, Avi Radko, Carrillo Andrew, Harper Nathan, Pauskar Merit, Sadam Maarja, Karki Tõnis, Krispin Tõnu, Kongo Ulvi-Kaire, Jermilova Tatiana, Rüütel Kristi, Talu Ave, Abel-Ollo Katri, Uusküla Anneli, Ahuja Sunil K, He Weijing, Lutsar Irja
Аннотация
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.
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.