The search for a genetic factor associating with immune restoration disease in HIV patients co-infected with Mycobacterium tuberculosis

Dis Markers. 2013;34(6):445-9. doi: 10.3233/DMA-130991.

Abstract

Background: Up to 43% of HIV-infected patients co-infected with Mycobacterium tuberculosis experience exacerbations of tuberculosis (TB) after commencing antiretroviral therapy (ART). These are termed immune restoration disease (IRD). It is unclear why individual susceptibility varies.

Objective: We investigate if single nucleotide polymorphisms (SNP) in genes encoding cytokines, chemokines and their receptors associate with development of an IRD event in patients of two different ethnicities.

Methods: DNA samples were available from small well-characterised groups of HIV patients treated in Cambodia (TB-IRD, n=17; HIV(+)TB(+) controls, n=55) and India (TB-IRD, n=19; HIV(+)TB(+) controls, n= 43). HIV patients with a TB diagnosis but no evidence of IRD were included to control for susceptibility to TB per se. Sixteen SNP implicated in inflammation or mycobacterial disease were genotyped.

Results: Susceptibility to TB-IRD associated with carriage of TNFA-1031*T (rs1799964; P=0.05) and SLC11A1 D543N*G (rs17235409; P=0.04) in Cambodian patients and carriage of IL18-607*G (rs1946518; P=0.02) and VDR FokI (F/f)*T (rs10735810; P=0.05) in Indian patients.

Conclusions: Associations between polymorphisms in immune-related genes and TB-IRD were found, but none were common across two ethnicities.

MeSH terms

  • Adolescent
  • Adult
  • Cambodia
  • Case-Control Studies
  • Chemokines / genetics
  • Coinfection / immunology
  • Female
  • Genetic Association Studies
  • HIV Infections / complications*
  • HIV Infections / immunology
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / genetics*
  • India
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis
  • Polymorphism, Single Nucleotide
  • Tuberculosis / complications*
  • Tuberculosis / immunology

Substances

  • Chemokines