The influence of host genetic factors on the susceptibility to HIV and HCV infections among intravenous drug users
Date
2014-03-25
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Abstract
Süstitavate narkootikumide kasutamine on maailmas toonud kaasa vere teel levivate viiruste (nt HIV ja HCV) kiire leviku. Eestis sai HIV-1 epideemia alguse 2000. aastal, kui Euroopas haruldane HIV-1 rekombinantne vorm CRF06_cpx sisenes süstivate narkomaanide (SN-de) populatsiooni ja hakkas seal kiiresti levima. HIV-i nakatumist mõjutavad mitmed faktorid, mille hulka kuuluvad ka inimese geneetilised faktorid. Neid on peamiselt uuritud viiruse levimisel seksuaalsel teel, kuid ei ole teada, kuidas samad geneetilised faktorid mõjutavad HIV-i nakatumist süstimise teel. Käesoleva uuringu eesmärgiks oli hinnata HIV-i koretseptori CCR5 ja tema ligandide (CCL3L1 ja CCL5) ning TLR3 geneetilise mitmekesisuse mõju HIV-i ja HCV-sse nakatumisele SN-de seas.
Selleks kaasati uuringusse 374 SN-i Eesti kahest süstlavahetuspunktist ja kolmest vanglast (aastatel 2006-2007) ning 345 SN-i ühest süstlavahetuspunktist (2010. aastal). Real-time PCR-ga määrati CCR5, CCL5 ja TLR3 ühenukleotiidsed polümorfismid ning CCL3L1 koopia arv. CCR5 ja CCL5 haplotüüpide määramisel kasutati varem väljatöötatud definitsioone.
Uuringus leiti, et CCR5 haplotüüp G*1 omas kaitsvat efekti HCV-sse nakatumise eest (ORkohandatud = 0,07; 95% CI = 0,03 – 0,20) võrreldes teiste haplotüüpidega SN-de seas. Lisaks, SN-del, kes omasid CCL5 haplotüüp D, olid väiksemad šanssid olla HCV-positiivsed (ORkohandatud = 0,12; 95% CI = 0,03 – 0,42) võrreldes nendega, kes seda haplotüüpi ei omanud. Samas nii CCR5 kui CCL5 hapoltüübid ei mõjutanud HIV-sse nakatumist. SN-del, kes omasid populatsiooni keskmisest kõrgemat CCL3L1 koopia arvu, olid väiksemad šanssid olla HIV-positiivsed (ORkohandatud = 0,20; 95% CI = 0,09 – 0,45) võrreldes madalama koopia arvuga SN-ga. CCL3L1 koopia arv ei mõjutanud HCV-sse nakatumist. TLR3 rs3775291 T-alleeli esinemine vähendas HIV-i nakatumist (ORkohandatud = 0,25; 95% CI = 0,07 – 0,87) võrreldes SN-dega, kes seda alleeli ei omanud. Kokkuvõtvalt, antud uuringu tulemused näitasid, et SN-de populatsioonis CCL3L1 ja TLR3 mitmekesisus mõjutab HIV-i nakatumist ning CCR5 ja CCL5 mitmekesisus HCV-sse nakatumist.
The injecting drug use and the spread of blood-borne viruses (e.g. HIV and HCV) due to contaminated syringes are a major concern worldwide. In Estonia, the HIV-1 epidemic started in 2000 when rare recombinant form CRF06_cpx entered into the intravenous drug users (IDUs) population. One of the factors that influence the susceptibility to HIV is host genetic factors. These factors have been studies mainly among persons infected or exposed by sexual transmission. How these factors influence the susceptibility to HIV among IDUs is largely unknown. The aim of current study was to assess the influence of genetic variability of HIV co-receptor CCR5 and its ligand (CCL3L1 and CCL5) and TLR3 on susceptibility to HIV and HCV in IDUs population. For that 374 IDUs were recruited from two syringe exchange programmes and three prisons (during 2006 – 2007) and 345 IDUs from one syringe exchange programmes (in 2010) in Estonia. The single nucleotide polymorphisms of CCR5, CCL5 and TLR3, and copy number of CCL3L1 were determined by real-time PCR. CCR5 and CCL5 halpotypes were defined using literature. The results showed that CCR5 haplotype G*1 had protective effect against the susceptibility to HCV (ORadjusted = 0.07; 95% CI = 0.03 – 0.20) compared to other haplotypes. In addition, IDUs who possessed CCL5 haplotype D had decreased odds of being HCV positive (ORadjusted = 0.12; 95% CI = 0.03 – 0.42) than IDUs without this haplotype. However, CCR5 and CCL5 haplotyped did not influence the susceptibility to HIV. IDUs who had higher CCL3L1 copy number than population median had decreased odds of being HIV positive (ORadjusted = 0.20; 95% CI = 0.09 – 0.45) compared to IDUs with lower copy number. The possession of TLR3 rs3775291 T allele gave a protective effect against HIV infection (ORadjusted = 0.25; 95% CI = 0.07 – 0.87) compared to IDUs not possessing this allele. In summary, current study showed that in IDUs population the variability of CCL3L1 and TLR3 influence the susceptibility to HIV, and the variability of CCR5 and CCL5 influence the susceptibility to HCV.
The injecting drug use and the spread of blood-borne viruses (e.g. HIV and HCV) due to contaminated syringes are a major concern worldwide. In Estonia, the HIV-1 epidemic started in 2000 when rare recombinant form CRF06_cpx entered into the intravenous drug users (IDUs) population. One of the factors that influence the susceptibility to HIV is host genetic factors. These factors have been studies mainly among persons infected or exposed by sexual transmission. How these factors influence the susceptibility to HIV among IDUs is largely unknown. The aim of current study was to assess the influence of genetic variability of HIV co-receptor CCR5 and its ligand (CCL3L1 and CCL5) and TLR3 on susceptibility to HIV and HCV in IDUs population. For that 374 IDUs were recruited from two syringe exchange programmes and three prisons (during 2006 – 2007) and 345 IDUs from one syringe exchange programmes (in 2010) in Estonia. The single nucleotide polymorphisms of CCR5, CCL5 and TLR3, and copy number of CCL3L1 were determined by real-time PCR. CCR5 and CCL5 halpotypes were defined using literature. The results showed that CCR5 haplotype G*1 had protective effect against the susceptibility to HCV (ORadjusted = 0.07; 95% CI = 0.03 – 0.20) compared to other haplotypes. In addition, IDUs who possessed CCL5 haplotype D had decreased odds of being HCV positive (ORadjusted = 0.12; 95% CI = 0.03 – 0.42) than IDUs without this haplotype. However, CCR5 and CCL5 haplotyped did not influence the susceptibility to HIV. IDUs who had higher CCL3L1 copy number than population median had decreased odds of being HIV positive (ORadjusted = 0.20; 95% CI = 0.09 – 0.45) compared to IDUs with lower copy number. The possession of TLR3 rs3775291 T allele gave a protective effect against HIV infection (ORadjusted = 0.25; 95% CI = 0.07 – 0.87) compared to IDUs not possessing this allele. In summary, current study showed that in IDUs population the variability of CCL3L1 and TLR3 influence the susceptibility to HIV, and the variability of CCR5 and CCL5 influence the susceptibility to HCV.
Description
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Keywords
narkomaanid, HIV, C-hepatiit, geenid, haplotüüp, Eesti, drug addicts, HIV, hepatitis C, genes, haplotype, Estonia