TY - JOUR
T1 - Association between TLR3 rs3775291 and resistance to HIV among highly exposed Caucasian intravenous drug users
AU - Huik, Kristi
AU - Avi, Radko
AU - Pauskar, Merit
AU - Kallas, Eveli
AU - Jõgeda, Ene Ly
AU - Karki, Tõnis
AU - Marsh, Kristina
AU - Des Jarlais, Don
AU - Uusküla, Anneli
AU - Lutsar, Irja
N1 - Funding Information:
The work was supported by European Union through the European Regional Development Fund; Estonian Science Foundation (Grants 8415 and 8856); Basic Financing and the Target Financing of Estonian Ministry of Education and Research (SF0180004s12); and Grant R01 DA003574 from the US National Institutes of Health.
PY - 2013/12
Y1 - 2013/12
N2 - 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. Materials and 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.
AB - 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. Materials and 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.
KW - Highly exposed HIV seronegatives
KW - Intravenous drug users
KW - Leu412Phe
KW - TLR3
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U2 - 10.1016/j.meegid.2013.08.008
DO - 10.1016/j.meegid.2013.08.008
M3 - Article
C2 - 23962581
AN - SCOPUS:84883805436
SN - 1567-1348
VL - 20
SP - 78
EP - 82
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
ER -