Susceptibility to Mycobacterium tuberculosis infection in HIV-positive patients is associated with CARD8 genetic variant

J Acquir Immune Defic Syndr. 2013 Jun 1;63(2):147-51. doi: 10.1097/QAI.0b013e31828f93bb.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / complications
  • AIDS-Related Opportunistic Infections / genetics*
  • Adult
  • Alleles
  • Brazil
  • CARD Signaling Adaptor Proteins / genetics*
  • Coinfection
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • HIV Infections / complications
  • HIV Infections / genetics*
  • Humans
  • Inflammasomes / genetics
  • Male
  • Mycobacterium tuberculosis
  • Neoplasm Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Tuberculosis / complications
  • Tuberculosis / genetics*

Substances

  • CARD Signaling Adaptor Proteins
  • CARD8 protein, human
  • Inflammasomes
  • Neoplasm Proteins