Association between TLR3 rs3775291 and resistance to HIV among highly exposed Caucasian intravenous drug users

Kristi Huik, Radko Avi, Merit Pauskar, Eveli Kallas, Ene Ly Jõgeda, Tõnis Karki, Kristina Marsh, Don Des Jarlais, Anneli Uusküla, Irja Lutsar

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish (US)
Pages (from-to)78-82
Number of pages5
JournalInfection, Genetics and Evolution
Volume20
DOIs
StatePublished - Jan 1 2013

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drug user
human immunodeficiency virus
Drug Users
HIV
drugs
Blood Donors
blood
HIV infections
alleles
HIV Infections
allele
Alleles
Tick-borne encephalitis virus
virus
DNA viruses
myocarditis
double-stranded RNA
Human immunodeficiency virus 1
Needle Sharing
Tick-Borne Encephalitis Viruses

Keywords

  • Highly exposed HIV seronegatives
  • Intravenous drug users
  • Leu412Phe
  • TLR3

ASJC Scopus subject areas

  • Microbiology
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Association between TLR3 rs3775291 and resistance to HIV among highly exposed Caucasian intravenous drug users. / Huik, Kristi; Avi, Radko; Pauskar, Merit; Kallas, Eveli; Jõgeda, Ene Ly; Karki, Tõnis; Marsh, Kristina; Des Jarlais, Don; Uusküla, Anneli; Lutsar, Irja.

In: Infection, Genetics and Evolution, Vol. 20, 01.01.2013, p. 78-82.

Research output: Contribution to journalArticle

Huik, Kristi ; Avi, Radko ; Pauskar, Merit ; Kallas, Eveli ; Jõgeda, Ene Ly ; Karki, Tõnis ; Marsh, Kristina ; Des Jarlais, Don ; Uusküla, Anneli ; Lutsar, Irja. / Association between TLR3 rs3775291 and resistance to HIV among highly exposed Caucasian intravenous drug users. In: Infection, Genetics and Evolution. 2013 ; Vol. 20. pp. 78-82.
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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. 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.",
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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

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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.

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