Susceptibility to Mycobacterium tuberculosis Infection in HIV-Positive Patients Is Associated With CARD8 Genetic Variant

Pontillo, Alessandra PhD*; Carvalho, Marcia S. BSc; Kamada, Anselmo J. BSc; Moura, Ronald BSc; Schindler, Haiana C. MD; Duarte, Alberto J. S.*; Crovella, Sergio

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 June 2013 - Volume 63 - Issue 2 - p 147–151
doi: 10.1097/QAI.0b013e31828f93bb
Rapid Communication

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.

*Laboratory of Medical Investigation in Dermatology and Immunodeficiency, LIM-56, Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil;

Department of Genetics, Federal University of Pernambuco, Recife, Brazil; and

Department of Immunology, Aggeu Magalhães Research Center-CPqAM/FIOCRUZ, Recife, Brazil.

Correspondence to: Alessandra Pontillo, Laboratory of Medical Investigation in Dermatology and Immunodeficiency, LIM-56, Faculty of Medicine, University of Sao Paulo, Av. Dr Eneas de Caravalho Aguiar, 500, 05403-000 Sao Paulo, Brazil (e-mail: pontillo.a@gmail.com).

Supported by the Pernambuco Research Foundation (FACEPE) (project number APQ-0757-2.02/10) and Sao Paulo Research foundation (FAPESP) (project number 09/53575–5). A.Pontillo was recipient of a visiting researcher grant from Brazilian National Council of Research and Technology (CNPq) (no. 311949/2011-8). We did not receive any funding for this work from any of the following organizations: National Institutes of Health, Wellcome Trust, Howard Hughes Medical Institute.

The authors have no conflicts of interest to disclose.

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Received November 09, 2012

Accepted February 12, 2013

© 2013 by Lippincott Williams & Wilkins