TY - JOUR
T1 - Common polymorphisms in the CD43 gene region are associated with tuberculosis disease and mortality
AU - Campo, Monica
AU - Randhawa, April K.
AU - Dunstan, Sarah
AU - Farrar, Jeremy
AU - Caws, Maxine
AU - Bang, Nguyen Duc
AU - Lan, Nguyen Ngoc
AU - Chau, Tran Thi Hong
AU - Horne, David J.
AU - Thuong, Nguyen Thuong
AU - Thwaites, Guy E.
AU - Hawn, Thomas R.
N1 - Publisher Copyright:
Copyright © 2015 by the American Thoracic Society.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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.
AB - 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.
KW - CD43
KW - Mortality
KW - Single-nucleotide polymorphism
KW - Tuberculosis
KW - Tuberculous meningitis
UR - http://www.scopus.com/inward/record.url?scp=84979960238&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84979960238&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2014-0114OC
DO - 10.1165/rcmb.2014-0114OC
M3 - Article
C2 - 25078322
AN - SCOPUS:84979960238
SN - 1044-1549
VL - 52
SP - 342
EP - 348
JO - American journal of respiratory cell and molecular biology
JF - American journal of respiratory cell and molecular biology
IS - 3
ER -
