title: Common polymorphisms in the CD43 gene region are associated with tuberculosis disease and mortality.
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.
authors: 1 University of Washington, Seattle, Washington.
authors: Monica
authors: M
authors: Campo
authors: April K
authors: AK
authors: Randhawa
authors: Sarah
authors: S
authors: Dunstan
authors: Jeremy
authors: J
authors: Farrar
authors: Maxine
authors: M
authors: Caws
authors: Nguyen Duc
authors: ND
authors: Bang
authors: Nguyen Ngoc
authors: NN
authors: Lan
authors: Tran Thi
authors: TT
authors: Hong Chau
authors: David J
authors: DJ
authors: Horne
authors: Nguyen Thuong
authors: NT
authors: Thuong
authors: Guy E
authors: GE
authors: Thwaites
authors: Thomas R
authors: TR
authors: Hawn
mesh_terms: D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D051917:Leukosialin / Q000235:genetics*; D009169:Mycobacterium tuberculosis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014390:Tuberculosis, Meningeal / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000235:genetics*
chemical_list: D051917:Leukosialin; C465014:SPN protein, human
keywords: CD43; mortality; single-nucleotide polymorphism; tuberculosis; tuberculous meningitis