Polymorphisms in TICAM2 and IL1B are associated with TB

Genes Immun. 2015 Mar;16(2):127-133. doi: 10.1038/gene.2014.77. Epub 2014 Dec 18.


Human genetic susceptibility for tuberculosis (TB) has been demonstrated by several studies, but few have examined the multiple innate and adaptive immunity genes comprehensively, age-specific effects and/or resistance to Mycobacterium tuberculosis (Mtb) infection (resistors (RSTRs)). We hypothesized that RSTRs, defined by a persistently negative tuberculin skin test, may have different genetic influences than Mtb disease. We examined 29 candidate genes in pathways that mediate immune responses to Mtb in subjects in a household contact study in Kampala, Uganda. We genotyped 546 haplotype-tagging single-nucleotide polymorphisms (SNPs) in 835 individuals from 481 families; 28.7% had TB, 10.5% were RSTRs, and the remaining 60.8% had latent Mtb infection. Among our most significant findings were SNPs in TICAM2 (P = 3.6 × 10(-6)) and IL1B (P = 4.3 × 10(-5)) associated with TB. Multiple SNPs in IL4 and TOLLIP were associated with TB (P < 0.05). Age-genotype interaction analysis revealed SNPs in IL18 and TLR6 that were suggestively associated with TB in children aged ⩽ 10 years (P = 2.9 × 10(-3)). By contrast, RSTR was associated with SNPs in NOD2, SLC6A3 and TLR4 (nominal P < 0.05); these genes were not associated with TB, suggesting distinct genetic influences. We report the first association between TICAM2 polymorphisms and TB and between IL18 and pediatric TB.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Interleukin-1beta / genetics*
  • Male
  • Polymorphism, Single Nucleotide
  • Tuberculosis / epidemiology
  • Tuberculosis / genetics*
  • Uganda / epidemiology
  • Young Adult


  • Adaptor Proteins, Signal Transducing
  • IL1B protein, human
  • Interleukin-1beta
  • TICAM2 protein, human