| Autor: |
Horne DJ, Randhawa AK, Chau TT, Bang ND, Yen NT, Farrar JJ, Dunstan SJ, Hawn TR, Horne, David J, Randhawa, April K, Chau, Tran T H, Bang, Nguyen D, Yen, Nguyen T B, Farrar, Jeremy J, Dunstan, Sarah J, Hawn, Thomas R |
| Zdroj: |
Journal of Infectious Diseases; 2/15/2012, Vol. 205 Issue 4, p586-594, 9p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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