Variants in toll-like receptor 9 gene influence susceptibility to tuberculosis in a Mexican population.
BACKGROUND
The control of Mycobacterium tuberculosis (Mtb) infection begins with the recognition of mycobacterial structural components by toll like receptors (TLRs) and other pattern recognition receptors. Our objective was to determine the influence of TLRs polymorphisms in the susceptibility to develop tuberculosis (TB) in Amerindian individuals from a rural area of Oaxaca, Mexico with high TB incidence.


METHODS
We carried out a case-control association community based study, genotyping 12 polymorphisms of TLR2, TLR4, TLR6 and TLR9 genes in 90 patients with confirmed pulmonary TB and 90 unrelated exposed but asymptomatic household contacts.


RESULTS
We found a significant increase in the frequency of the allele A of the TLR9 gene polymorphism rs352139 (A>G) in the group of TB patients (g.f. = 0.522) when compared with controls (g.f. = 0.383), (Pcorr = 0.01, OR = 1.75). Under the recessive model (A/G + A/A vs G/G) this polymorphism was also significantly associated with TB (Pcorr = 0.01, OR= 2.37). The association of the SNP rs352139 was statistically significant after adjustment by age, gender and comorbidities by regression logistic analysis (Dominant model: p value = 0.016, OR = 2.31; Additive model: p value = 0.023, OR = 1.68). The haplotype GAA of TLR9 SNPs was also associated with TB susceptibility (Pcorr = 0.02). Differences in the genotype or allele frequencies of TLR2, TLR4 and TLR6 polymorphisms between TB patients and healthy contacts were not detected.


CONCLUSIONS
Our study suggests that the allele A of the intronic polymorphism rs352139 on TLR9 gene might contribute to the risk of developing TB in Mexican Amerindians.
Department of Immunolgy, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Mexico City, 14080, Mexico. cegarsan@netscape.net.
Diana
D
Torres-García
Alfredo
A
Cruz-Lagunas
Ma Cecilia
MC
García-Sancho Figueroa
Rosario
R
Fernández-Plata
Renata
R
Baez-Saldaña
Criselda
C
Mendoza-Milla
Rodrigo
R
Barquera
Aida
A
Carrera-Eusebio
Salomón
S
Ramírez-Bravo
Lizeth
L
Campos
Javier
J
Angeles
Gilberto
G
Vargas-Alarcón
Julio
J
Granados
Radha
R
Gopal
Shabaana A
SA
Khader
Edmond J
EJ
Yunis
Joaquin
J
Zuñiga
D000328:Adult; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008800:Mexico; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D051216:Toll-Like Receptor 6 / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000235:genetics*; D014376:Tuberculosis / Q000235:genetics*
C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495368:TLR6 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051217:Toll-Like Receptor 9