Variants in toll-like receptor 9 gene influence susceptibility to tuberculosis in a Mexican population
Por:
Torres-García D., Cruz-Lagunas A., Figueroa, MCGS, 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., Zuniga, JQ
Publicada:
21 sep 2013
Resumen:
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. © 2013 Torres-García et al.; licensee BioMed Central Ltd.
Filiaciones:
Department of Immunolgy, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Mexico City, 14080, Mexico
Department of Epidemiology and Social Sciences, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
Department of Tuberculosis, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
Department of Pulmonary Fibrosis, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
Molecular Genetics Laboratory, National School of Anthropology and History, Mexico City, Mexico
Jurisdicción Sanitaria No. 3 de Tuxtepec, Servicios de Salud del Estado de Oaxaca, Oaxaca, Mexico
Department of Genomics, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
Department of Transplants, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Division of Infectious Diseases, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
All Open Access, Gold
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