A CCL5 Haplotype Is Associated with Low Seropositivity Rate of HCV Infection in People Who Inject Drugs.
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% co-infected. 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.
Department of Microbiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu 50411, Estonia.
Kristi
K
Huik
Department of Microbiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu 50411, Estonia.
Radko
R
Avi
Department of Microbiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu 50411, Estonia.
Merit
M
Pauskar
Department of Microbiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu 50411, Estonia.
Eveli
E
Kallas
Department of Microbiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu 50411, Estonia.
Ene-Ly
EL
Jõgeda
Department of Microbiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu 50411, Estonia.
Tõnis
T
Karki
National Institute for Health Development, Tallinn 11619, Estonia.
Kristi
K
Rüütel
Institute of Family Medicine and Public Health, University of Tartu, Tartu 50411, Estonia.
Ave
A
Talu
National Institute for Health Development, Tallinn 11619, Estonia.
Katri
K
Abel-Ollo
Institute of Family Medicine and Public Health, University of Tartu, Tartu 50411, Estonia.
Anneli
A
Uusküla
Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, United States of America.|Veterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Texas 78229, United States of America.
Andrew
A
Carrillo
Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, United States of America.|Veterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Texas 78229, United States of America.
Sunil K
SK
Ahuja
Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, United States of America.|Veterans Administration Center for Personalized Medicine, South Texas Veterans Health Care System, San Antonio, Texas 78229, United States of America.
Weijing
W
He
Department of Microbiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu 50411, Estonia.
Irja
I
Lutsar
D000328:Adult; D000483:Alleles; D018946:Chemokine CCL5 / Q000235:genetics*; D060085:Coinfection / Q000453:epidemiology / Q000235:genetics / Q000821:virology; D055030:Drug Users / Q000706:statistics & numerical data; D004957:Estonia / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics; D006679:HIV Seropositivity / Q000453:epidemiology* / Q000235:genetics / Q000821:virology; D006239:Haplotypes; D006526:Hepatitis C / Q000453:epidemiology* / Q000235:genetics / Q000821:virology; D006801:Humans; D016015:Logistic Models; D008297:Male; D020641:Polymorphism, Single Nucleotide; D019713:Receptors, CCR5 / Q000235:genetics; D015819:Substance Abuse, Intravenous; D044465:White People / Q000235:genetics
C483024:CCL5 protein, human; C584933:CCR5 protein, human; D018946:Chemokine CCL5; D019713:Receptors, CCR5