Endosomal toll-like receptor gene polymorphisms and susceptibility to HIV and HCV co-infection - Differential influence in individuals with distinct ethnic background

Hum Immunol. 2017 Feb;78(2):221-226. doi: 10.1016/j.humimm.2017.01.001. Epub 2017 Jan 4.

Abstract

The genetic background of human populations can influence the susceptibility and outcome of infection diseases. Toll-like receptors (TLRs) have been previously associated with susceptibility to human immunodeficiency virus (HIV) infection, disease progression and hepatitis C, virus (HCV) co-infection in different populations, although mostly in Europeans. In this study, we investigated the genetic role of endosomal TLRs on susceptibility to HIV infection and HCV co-infection through the analysis of TLR7 rs179008, TLR8 rs3764880, TLR9 rs5743836 and TLR9 rs352140 polymorphisms in 789 Brazilian individuals (374 HIV+ and 415 HIV-), taking into account their ethnic background. Amongst the 357 HIV+ individuals with available data concerning HCV infection, 98 were positive. In European descendants, the TLR9 rs5743836 C carriers displayed a higher susceptibility to HIV infection [dominant, Odds Ratio (OR)=1.53; 95% CI: 1.05-2.23; P=0.027]. In African descendants, TLR9 rs5743836 CT genotype was associated with protection to HIV infection (codominant, OR=0.51; 95% CI: 0.30-0.87; P=0.013). Also, the TLR9 rs352140 AA variant genotype was associated with susceptibility to HIV+/HCV+ co-infection in African descendants (recessive, OR=2.92; 95% CI: 1.22-6.98, P=0.016). These results are discussed in the context of the different ethnic background of the studied individuals highlighting the influence of this genetic/ethnic background on the susceptibility to HIV infection and HIV/HCV co-infection in Brazilian individuals.

Keywords: Ethnic background; HCV; HIV-1; Susceptibility; TLRs polymorphisms.

MeSH terms

  • Adult
  • African Continental Ancestry Group
  • Brazil
  • Coinfection
  • Endosomes / metabolism
  • European Continental Ancestry Group
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • HIV Infections / genetics*
  • Hepatitis C / genetics*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Toll-Like Receptor 7 / genetics*
  • Toll-Like Receptor 8 / genetics*
  • Toll-Like Receptor 9 / genetics*

Substances

  • TLR7 protein, human
  • TLR8 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Toll-Like Receptor 9