Variants in toll-like receptors 2 and 9 influence susceptibility to pulmonary tuberculosis in Caucasians, African-Americans, and West Africans.
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 that associated 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.
Velez
Digna Rosa
DR
Department of Human Genetics, Dr. John T. Macdonald Foundation, Miller School of Medicine, University of Miami, Miami, FL 33136, USA. dvelez@med.miami.edu
Wejse
Christian
C
Stryjewski
Martin E
ME
Abbate
Eduardo
E
Hulme
William F
WF
Myers
Jamie L
JL
Estevan
Rosa
R
Patillo
Sara G
SG
Olesen
Rikke
R
Tacconelli
Alessandra
A
Sirugo
Giorgio
G
Gilbert
John R
JR
Hamilton
Carol D
CD
Scott
William K
WK
D001741:Black or African American / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006169:Guinea-Bissau; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051217:Toll-Like Receptor 9 / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000208:ethnology / Q000235:genetics*; D014481:United States; D044465:White People / Q000235:genetics*
C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051217:Toll-Like Receptor 9