title: Susceptibility to Mycobacterium tuberculosis infection in HIV-positive patients is associated with CARD8 genetic variant.
abstract: HLA and other genetic variants, playing an important role in innate and adaptive immunity, are known to influence tuberculosis (TB) development in HIV-1-positive (HIV+) patients. Because inflammasome genes contribute to HIV-1 susceptibility, we investigated the possible association between polymorphisms in inflammasome genes with HIV-1 and Mycobacterium tuberculosis coinfection (HIV+TB+) in a case/control cohort of Brazilian individuals. Nineteen single-nucleotide polymoprhims in 8 inflammasome genes (NLRP1, NLRP3, AIM2, CARD8, CASP1, IL1B, IL1R, and HSP90) were analyzed in HIV+TB+ Brazilian patients (from Recife, Pernambuco). CARD8 rs6509365 polymorphism was associated with HIV+TB+ (P = 5 × 10(-5)), suggesting a predisposing role of this variant in M. tuberculosis susceptibility in HIV+ subjects (odds ratio = 2.45). This effect is even strong when this allele is combined to CARD8 rs2043211 single-nucleotide polymoprhim. The results of this study support the novel association between CARD8 gene and HIV+TB+ coinfection, demonstrating that inflammasome genetics could influence HIV-1 infection and the development of opportunistic infection.
authors.affiliation: Laboratory of Medical Investigation in Dermatology and Immunodeficiency, LIM-56, Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil. pontillo.a@gmail.com
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pontillo
authors.forename: Marcia S
authors.initials: MS
authors.lastname: Carvalho
authors.forename: Anselmo J
authors.initials: AJ
authors.lastname: Kamada
authors.forename: Ronald
authors.initials: R
authors.lastname: Moura
authors.forename: Haiana C
authors.initials: HC
authors.lastname: Schindler
authors.forename: Alberto J S
authors.initials: AJ
authors.lastname: Duarte
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000235:genetics*; D000328:Adult; D000483:Alleles; D001938:Brazil; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D060085:Coinfection; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000150:complications / Q000235:genetics*; D006801:Humans; D058847:Inflammasomes / Q000235:genetics; D008297:Male; D009169:Mycobacterium tuberculosis; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014376:Tuberculosis / Q000150:complications / Q000235:genetics*
chemical_list: D053468:CARD Signaling Adaptor Proteins; C455623:CARD8 protein, human; D058847:Inflammasomes; D009363:Neoplasm Proteins