Variants in toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans

Digna Rosa Velez, Christian Wejse, Martin E. Stryjewski., Eduardo Abbate, William F. Hulme, Jamie L. Myers, Rosa Estevan, Sara G. Patillo, Rikke Olesen, Alessandra Tacconelli, Giorgio Sirugo, John Gilbert, Carol D. Hamilton, William K Scott

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122 Citations (Scopus)

Abstract

Tuberculosis (TB) is a global public health problem and a source of preventable deaths each year, with 8.8 million new cases of TB and 1.6 million deaths worldwide in 2005. Approximately, 10% of infected individuals develop pulmonary or extrapulmonary TB, suggesting that host defense factors influence development of active disease. Toll-like receptor' (TLR) polymorphisms have been associated with regulation of TLR expression and development of active TB. In the present study, 71 polymorphisms in TLR1, TLR2, TLR4, TLR6, and TLR9 were examined from 474 (295 cases and 179 controls) African-Americans, 381 (237 cases and 144 controls) Caucasians, and from 667 (321 cases and 346 controls) Africans from Guinea-Bissau for association with pulmonary TB using generalized estimating equations and logistic regression. Statistically significant associations were observed across populations at TLR9 and TLR2. The strongest evidence for association came at an insertion (I)/ deletion (D) polymorphism (-196 to -174) in TLR2 thatassociated with TB in both Caucasians (II vs. ID&DD, OR = 0.41 [95% CI 0.24-0.68], p = 0.0007) and Africans (II vs. ID&DD, OR = 0.70 [95% CI 0.51-0.95], p = 0.023). Our findings in three independent population samples indicate that variations in TLR2 and TLR9 might play important roles in determining susceptibility to TB.

Original languageEnglish
Pages (from-to)65-73
Number of pages9
JournalHuman Genetics
Volume127
Issue number1
DOIs
StatePublished - Jan 1 2010

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Toll-Like Receptor 9
Toll-Like Receptor 2
Pulmonary Tuberculosis
African Americans
Tuberculosis
Toll-Like Receptors
Guinea-Bissau
Population
Public Health
Logistic Models
Lung

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Variants in toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans. / Velez, Digna Rosa; Wejse, Christian; Stryjewski., Martin E.; Abbate, Eduardo; Hulme, William F.; Myers, Jamie L.; Estevan, Rosa; Patillo, Sara G.; Olesen, Rikke; Tacconelli, Alessandra; Sirugo, Giorgio; Gilbert, John; Hamilton, Carol D.; Scott, William K.

In: Human Genetics, Vol. 127, No. 1, 01.01.2010, p. 65-73.

Research output: Contribution to journalArticle

Velez, DR, Wejse, C, Stryjewski., ME, Abbate, E, Hulme, WF, Myers, JL, Estevan, R, Patillo, SG, Olesen, R, Tacconelli, A, Sirugo, G, Gilbert, J, Hamilton, CD & Scott, WK 2010, 'Variants in toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans', Human Genetics, vol. 127, no. 1, pp. 65-73. https://doi.org/10.1007/s00439-009-0741-7
Velez, Digna Rosa ; Wejse, Christian ; Stryjewski., Martin E. ; Abbate, Eduardo ; Hulme, William F. ; Myers, Jamie L. ; Estevan, Rosa ; Patillo, Sara G. ; Olesen, Rikke ; Tacconelli, Alessandra ; Sirugo, Giorgio ; Gilbert, John ; Hamilton, Carol D. ; Scott, William K. / Variants in toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans. In: Human Genetics. 2010 ; Vol. 127, No. 1. pp. 65-73.
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