title: Endosomal toll-like receptor gene polymorphisms and susceptibility to HIV and HCV co-infection - Differential influence in individuals with distinct ethnic background.
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.
authors.affiliation: Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Valverde-Villegas
authors.affiliation: Universidade Luterana do Brasil (ULBRA), Canoas, Rio Grande do Sul, Brazil; INSERM U1026, Tissue Bioengineering, Université de Bordeaux, Bordeaux F-33076, France.
authors.forename: Bruno Paiva
authors.initials: BP
authors.lastname: Dos Santos
authors.affiliation: Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Rúbia Marília
authors.initials: RM
authors.lastname: de Medeiros
authors.affiliation: Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Vanessa Suñé
authors.initials: VS
authors.lastname: Mattevi
authors.affiliation: Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Rosmeri Kuhmmer
authors.initials: RK
authors.lastname: Lazzaretti
authors.affiliation: Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sprinz
authors.affiliation: Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Regina
authors.initials: R
authors.lastname: Kuhmmer
authors.affiliation: Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: jabchies@terra.com.br.
authors.forename: José Artur Bogo
authors.initials: JA
authors.lastname: Chies
mesh_terms: D000328:Adult; D044383:Black People; D001938:Brazil; D060085:Coinfection; D011992:Endosomes / Q000378:metabolism; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000235:genetics*; D006526:Hepatitis C / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051199:Toll-Like Receptor 7 / Q000235:genetics*; D051200:Toll-Like Receptor 8 / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*; D044465:White People
chemical_list: C495348:TLR7 protein, human; C495349:TLR8 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9
keywords: Ethnic background; HCV; HIV-1; Susceptibility; TLRs polymorphisms