Variants in toll-like receptor 9 gene influence susceptibility to tuberculosis in a Mexican population

Diana Torres-García, Alfredo Cruz-Lagunas, Ma C. García-Sancho Figueroa, Rosario Fernández-Plata, Renata Baez-Saldaña, Criselda Mendoza-Milla, Rodrigo Barquera, Aida Carrera-Eusebio, Salomón Ramírez-Bravo, Lizeth Campos, Javier Angeles, Gilberto Vargas-Alarcón, Julio Granados, Radha Gopal, Shabaana A. Khader, Edmond J. Yunis, Joaquin Zuñiga

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33 Scopus citations

Abstract

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.

Original languageEnglish
Article number220
JournalJournal of Translational Medicine
Volume11
Issue number1
DOIs
StatePublished - Sep 21 2013
Externally publishedYes

Keywords

  • Gene polymorphisms
  • Susceptibility
  • TLR9
  • TLRs
  • Tuberculosis
  • rs352139

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    Torres-García, D., Cruz-Lagunas, A., García-Sancho Figueroa, M. C., Fernández-Plata, R., Baez-Saldaña, R., Mendoza-Milla, C., Barquera, R., Carrera-Eusebio, A., Ramírez-Bravo, S., Campos, L., Angeles, J., Vargas-Alarcón, G., Granados, J., Gopal, R., Khader, S. A., Yunis, E. J., & Zuñiga, J. (2013). Variants in toll-like receptor 9 gene influence susceptibility to tuberculosis in a Mexican population. Journal of Translational Medicine, 11(1), [220]. https://doi.org/10.1186/1479-5876-11-220