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

• Published in: Human immunology 2017-02, Vol.78 (2), p.221-226
• Main Authors: Valverde-Villegas, Jacqueline M, Paiva dos Santos, Bruno, Marília de Medeiros, Rúbia, Suñé Mattevi, Vanessa, Kuhmmer Lazzaretti, Rosmeri, Sprinz, Eduardo, Kuhmmer, Regina, Artur Bogo Chies, José
• Format: Article
• Language: English
• Subjects: Adult; African Continental Ancestry Group; Allergy and Immunology; Brazil; Coinfection; Endosomes - metabolism; Ethnic background; European Continental Ancestry Group; Gene Frequency; Genetic Predisposition to Disease; Genotype; HCV; Hepatitis C - genetics; HIV Infections - genetics; HIV-1; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Susceptibility; TLRs polymorphisms; Toll-Like Receptor 7 - genetics; Toll-Like Receptor 8 - genetics; Toll-Like Receptor 9 - genetics
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2017.01.001

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.