Variants in toll-like receptor 9 gene influence susceptibility to tuberculosis in a Mexican population
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- 作者：Diana Torres-García (1)
Alfredo Cruz-Lagunas (1)
Ma Cecilia García-Sancho Figueroa (2)
Rosario Fernández-Plata (2)
Renata Baez-Salda?a (3)
Criselda Mendoza-Milla (4)
Rodrigo Barquera (5)
Aida Carrera-Eusebio (6)
Salomón Ramírez-Bravo (6)
Lizeth Campos (1)
Javier Angeles (7)
Gilberto Vargas-Alarcón (7)
Julio Granados (8)
Radha Gopal (9)
Shabaana A Khader (9)
Edmond J Yunis (10)
Joaquin Zu?iga (1) - 关键词：Tuberculosis ; rs352139 ; TLRs ; Gene polymorphisms ; Susceptibility ; TLR9
- 刊名：Journal of Translational Medicine
- 出版年：2013
- 出版时间：December 2013
- 年：2013
- 卷：11
- 期：1
- 全文大小：231 KB
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Alfredo Cruz-Lagunas (1)
Ma Cecilia García-Sancho Figueroa (2)
Rosario Fernández-Plata (2)
Renata Baez-Salda?a (3)
Criselda Mendoza-Milla (4)
Rodrigo Barquera (5)
Aida Carrera-Eusebio (6)
Salomón Ramírez-Bravo (6)
Lizeth Campos (1)
Javier Angeles (7)
Gilberto Vargas-Alarcón (7)
Julio Granados (8)
Radha Gopal (9)
Shabaana A Khader (9)
Edmond J Yunis (10)
Joaquin Zu?iga (1)
1. Department of Immunolgy, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Mexico City, 14080, Mexico
2. Department of Epidemiology and Social Sciences, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
3. Department of Tuberculosis, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
4. Department of Pulmonary Fibrosis, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
5. Molecular Genetics Laboratory, National School of Anthropology and History, Mexico City, Mexico
6. Jurisdicción Sanitaria No. 3 de Tuxtepec, Servicios de Salud del Estado de Oaxaca, Oaxaca, Mexico
7. Department of Genomics, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
8. Department of Transplants, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
9. Division of Infectious Diseases, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA
10. Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA - ISSN：1479-5876
文摘
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.