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Common polymorphisms in the PKP3-SIGIRR-TMEM16J gene region are associated with susceptibility to tuberculosis.
Title | Common polymorphisms in the PKP3-SIGIRR-TMEM16J gene region are associated with susceptibility to tuberculosis. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Horne, DJ, Randhawa, AK, Chau, TTH, Bang, ND, Yen, NTB, Farrar, JJ, Dunstan, SJ, Hawn, TR |
Journal | J Infect Dis |
Volume | 205 |
Issue | 4 |
Pagination | 586-94 |
Date Published | 2012 Feb 15 |
ISSN | 1537-6613 |
Keywords | Adolescent, Adult, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Male, Membrane Proteins, Middle Aged, Plakophilins, Polymorphism, Single Nucleotide, Receptors, Interleukin-1, Tuberculosis, Meningeal, Tuberculosis, Pulmonary, Vietnam, Young Adult |
Abstract | BACKGROUND: Tuberculosis has been associated with genetic variation in host immunity. We hypothesized that single-nucleotide polymorphisms (SNPs) in SIGIRR, a negative regulator of Toll-like receptor/IL-1R signaling, are associated with susceptibility to tuberculosis. METHODS: We used a case-population study design in Vietnam with cases that had either tuberculous meningitis or pulmonary tuberculosis. We genotyped 6 SNPs in the SIGIRR gene region (including the adjacent genes PKP3 and TMEM16J) in a discovery cohort of 352 patients with tuberculosis and 382 controls. Significant associations were genotyped in a validation cohort (339 patients with tuberculosis, 376 controls). RESULTS: Three SNPs (rs10902158, rs7105848, rs7111432) were associated with tuberculosis in discovery and validation cohorts. The polymorphisms were associated with both tuberculous meningitis and pulmonary tuberculosis and were strongest with a recessive genetic model (odds ratios, 1.5-1.6; P = .0006-.001). Coinheritance of these polymorphisms with previously identified risk alleles in Toll-like receptor 2 and TIRAP was associated with an additive risk of tuberculosis susceptibility. CONCLUSIONS: These results demonstrate a strong association of SNPs in the PKP3-SIGIRR-TMEM16J gene region and tuberculosis in discovery and validation cohorts. To our knowledge, these are the first associations of polymorphisms in this region with any disease. |
DOI | 10.1093/infdis/jir785 |
Alternate Journal | J. Infect. Dis. |
PubMed ID | 22223854 |