期刊
PLOS ONE
卷 11, 期 6, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0156850
关键词
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资金
- European Union through the European Regional Development Fund
- Basic Financing
- Target Financing [SF0180004s12]
- Institutional research funding of Estonian Ministry of Education and Research [IUT34-24, IUT34-17]
- European Commission - project Expanding Network for Comprehensive and Coordinated Action on HIV/AIDS prevention among IDUs and Bridging Population [2005305]
- Global Fund
- Tuberculosis and Malaria Program Scaling up the response to HIV in Estonia
- National HIV/AIDS Strategy
- US Civilian Research Development Foundation [ESX0-2722-TA-06]
- US National Institutes of Health
- National Institute on Drug Abuse [R01DA03574]
- Archimedes Foundation and Norwegian Financial Mechanism/EEA [EE0016]
- Veterans Affairs (VA) Center for AIDS and HIV Infection and VA Center for Personalized Medicine of the South Texas Veterans Health Care System
- National Institutes of Health MERIT grant [R37AI046326]
- Doris Duke Distinguished Clinical Scientist Award
- VA MERIT award
- Elizabeth Glaser Pediatric AIDS Foundation
- Burroughs Welcome Clinical Scientist Award in Translational Research
- Senior Scholar Award from the Max and Minnie Tomerlin Voelcker Fund
Objective The role of CC chemokine receptor 5 (CCR5) and its ligand CCL5 on the pathogenesis of HIV infection has been well studied but not for HCV infection. Here, we investigated whether CCL5 haplotypes influence HIV and HCV seropositivity among 373 Caucasian people who inject drugs (PWID) from Estonia. Methods Study included 373 PWID; 56% were HIV seropositive, 44% HCV seropositive and 47% coinfected. Four CCL5 haplotypes (A-D) were derived from three CCL5 polymorphisms (rs2107538/rs2280788/rs2280789) typed by Taqman allelic discrimination assays. The data of CCR5 haplotypes were used from our previous study. The association between CCL5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis. Results Possessing CCL5 haplotype D (defined by rs2107538A/rs2280788G/rs2280789C) decreased the odds of HCV seropositivity compared to those not possessing it (OR = 0.19; 95% CI 0.09-0.40), which remained significant after adjustment to co-variates (OR = 0.08; 95% CI 0.02-0.29). An association of this haplotype with HIV seropositivity was not found. In step-wise logistic regression with backward elimination CCL5 haplotype D and CCR5 HHG*1 had reduced odds for HCV seropositivity (OR = 0.28 95% CI 0.09-0.92; OR = 0.23 95% CI 0.08-0.68, respectively) compared to those who did not possess these haplotypes, respectively. Conclusions Our results suggest that among PWID CCL5 haplotype D and CCR5 HHG*1 independently protects against HCV. Our findings highlight the importance of CCL5 genetic variability and CCL5-CCR5 axis on the susceptibility to HCV.
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