title: Association between TLR3 rs3775291 and resistance to HIV among highly exposed Caucasian intravenous drug users.
abstract: BACKGROUND
  TLR3 recognizes dsRNA and triggers immune responses against RNA and DNA viruses. A polymorphism in TLR3, rs3775291 (Leu412Phe), has been associated with the increased susceptibility to enteroviral myocarditis, protection against tick-borne encephalitis virus and HIV-1 infection. We investigated Caucasian intravenous drug users (IDUs) and blood donors in order to evaluate the associations between TLR3 genotypes and susceptibility to HIV infection.
  
  
  METHODS
  A total of 345 Caucasian IDUs were recruited, 50% of them were HIV positive, 89% HCV and 77% HBV positive. Based on their history of needle sharing, 20 of the HIV negative IDUs were classified as highly exposed HIV seronegatives (HESNs), 68 as non-HESNs and 85 as unexposed. The control group consisting of 497 blood donors tested negative for all three viruses. TLR3 rs3775291 were determined by using TaqMan Allelic Discrimination Assay.
  
  
  RESULTS
  The TLR3 rs3775291 T allele frequency was similar among the HIV negative and HIV positive IDUs and blood donors - 36%, 31% and 34%, respectively. The frequency of persons possessing at least one TLR3 rs3775291 T allele was significantly higher in HESNs compared with blood donors and HIV positive IDUs (80% vs. 55%; p=0.037 and 80% vs. 53%; p=0.031, respectively). In the univariate analysis, persons who possessed at least one T allele had reduced odds of being HIV seropositive (OR=0.29, 95% CI=0.09-0.90). This association remained significant (OR=0.25, 95% CI=0.07-0.87) after the adjustment for other co-variates (HCV, HBV serostatus and duration of intravenous drug use).
  
  
  CONCLUSIONS
  The TLR3 rs3775291 T allele has a protective effect against HIV infection among HESNs IDUs.
authors: Department of Microbiology, Faculty of Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia. Electronic address: kristi.huik@ut.ee.
authors: Kristi
authors: K
authors: Huik
authors: Radko
authors: R
authors: Avi
authors: Merit
authors: M
authors: Pauskar
authors: Eveli
authors: E
authors: Kallas
authors: Ene-Ly
authors: EL
authors: Jõgeda
authors: Tõnis
authors: T
authors: Karki
authors: Kristina
authors: K
authors: Marsh
authors: Don
authors: D
authors: Des Jarlais
authors: Anneli
authors: A
authors: Uusküla
authors: Irja
authors: I
authors: Lutsar
mesh_terms: D000328:Adult; D001782:Blood Donors; D055030:Drug Users; D004957:Estonia; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000635:transmission; D006679:HIV Seropositivity / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D015819:Substance Abuse, Intravenous / Q000235:genetics / Q000276:immunology / Q000821:virology*; D011795:Surveys and Questionnaires; D051196:Toll-Like Receptor 3 / Q000235:genetics* / Q000276:immunology*; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3
keywords: Highly exposed HIV seronegatives; Intravenous drug users; Leu412Phe; TLR3
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