Common polymorphisms in the CD43 gene region are associated with tuberculosis disease and mortality

Monica Campo, April K. Randhawa, Sarah Dunstan, Jeremy Farrar, Maxine Caws, Nguyen Duc Bang, Nguyen Ngoc Lan, Tran Thi Hong Chau, David J. Horne, Nguyen Thuong Thuong, Guy E. Thwaites, Thomas R. Hawn

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

CD43, a surface glycoprotein, regulates Mycobacterium tuberculosis macrophage binding, replication, and proinflammatory cytokine induction in a murine model. We hypothesized that single-nucleotide polymorphisms (SNPs) in the CD43 gene region are associated with human tuberculosis (TB) susceptibility. We performed a case-population study in discovery (352 TB cases and 382 control subjects) and validation cohorts (339 TB cases and 376 control subjects). We examined whether 11 haplotype-tagging SNPs in the CD43 gene region were associated with tuberculous meningitis (TBM) and pulmonary TB (PTB) in Vietnam. Three SNPs from the CD43 gene region were associated with TB susceptibility with a genotypic model. The association fit a recessive genetic model and was greater for TBM than for PTB (for TBM: rs4788172, odds ratio [OR], 1.64; 95% confidence interval [CI], 1.04-2.59, rs17842268 [OR, 2.20; 95% CI, 1.29-3.76, and rs12596308 [OR, 2.38; 95% CI, 1.47-3.89]). Among TBM cases, rs17842268 was associated with decreased survival (hazard ratio, 2.7; 95% CI, 1.1-6.5; P = 0.011). In addition, rs12596308 and rs17842268 were associated with focal neurologic deficit at TBM presentation. Our data suggest that CD43 polymorphisms are associated with TB susceptibility, disease manifestations, and worse outcomes. To our knowledge, this is the first report that links CD43 genetic variants with susceptibility and outcome from a disease.

Original languageEnglish (US)
Pages (from-to)342-348
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume52
Issue number3
DOIs
StatePublished - Mar 1 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2015 by the American Thoracic Society.

Keywords

  • CD43
  • Mortality
  • Single-nucleotide polymorphism
  • Tuberculosis
  • Tuberculous meningitis

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