Single Nucleotide Polymorphisms in TLR4 Affect Susceptibility to Tuberculosis in Mexican Population from the State of Veracruz
Tuberculosis is still a global public health problem, with an estimated 10 million new cases and 1.6 million deaths in 2017. Of all humans infected with M. tuberculosis, only 10-15% will develop active tuberculosis disease during their lifetime, and data suggest that along with environmental factors...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2020/2965697 |
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| author | Enrique Ortega Sujhey Hernández-Bazán Beatriz Sánchez-Hernández Ileana Licona-Limón Javier Fuentes-Dominguez |
| author_facet | Enrique Ortega Sujhey Hernández-Bazán Beatriz Sánchez-Hernández Ileana Licona-Limón Javier Fuentes-Dominguez |
| author_sort | Enrique Ortega |
| collection | DOAJ |
| description | Tuberculosis is still a global public health problem, with an estimated 10 million new cases and 1.6 million deaths in 2017. Of all humans infected with M. tuberculosis, only 10-15% will develop active tuberculosis disease during their lifetime, and data suggest that along with environmental factors, genetic factors influence susceptibility to develop active disease. Toll-like receptors (TLRs) are pattern recognition receptors that play a central role in the initiation and shaping of adaptive immune responses, and several TLRs have been shown to recognize mycobacterial components. In this work, we performed a case-control study to determine if common single nucleotide polymorphisms (SNPs) in genes encoding TLRs 1, 2, 4, 6, and 10 are associated with susceptibility to develop active tuberculosis in population from the state of Veracruz, Mexico. The study included 279 cases and 569 controls. The results show that the frequency of two SNPs in TLR4 was significantly higher in controls than in tuberculosis patients. The minor allele (G) of rs4986790 in TLR4 (D299G) decreased the risk of active tuberculosis in the allelic (A vs. G, OR=0.31, 95%CI=0.09‐0.81, p=0.01) and in the dominant genetic model (AA vs. GG+AG, OR=0.26, 95%CI=0.09‐0.77, p=0.02). Similarly, the minor allele (T) of rs4986791 in TLR4 (T399I) decreased the risk of active disease in the allelic model (C vs. T, OR=0.29, 95%CI=0.10‐0.90, p=0.03). We did not find an association of SNPs in TLR1 (N248S), TLR2 (R753Q), TLR6 (S249P), and TLR10 (A153S and V298I) with tuberculosis disease. These results suggest that in this population, genetic variants of TLR4 affect the susceptibility for suffering active tuberculosis disease. |
| format | Article |
| id | doaj-art-1b3a9ca6b6a74ead986095c8e3ae0f9c |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-1b3a9ca6b6a74ead986095c8e3ae0f9c2025-02-03T06:43:50ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/29656972965697Single Nucleotide Polymorphisms in TLR4 Affect Susceptibility to Tuberculosis in Mexican Population from the State of VeracruzEnrique Ortega0Sujhey Hernández-Bazán1Beatriz Sánchez-Hernández2Ileana Licona-Limón3Javier Fuentes-Dominguez4Department of Immunology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, CP 04510 CDMX, MexicoDepartment of Immunology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, CP 04510 CDMX, MexicoDepartment of Genetics, Instituto Nacional de Ciencias Médicas y de la Nutrición Salvador Zubirán, CDMX, MexicoDepartment of Immunology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, CP 04510 CDMX, MexicoProgram of Micobacteriosis. Servicios de Salud de Veracruz, Xalapa, Veracruz, MexicoTuberculosis is still a global public health problem, with an estimated 10 million new cases and 1.6 million deaths in 2017. Of all humans infected with M. tuberculosis, only 10-15% will develop active tuberculosis disease during their lifetime, and data suggest that along with environmental factors, genetic factors influence susceptibility to develop active disease. Toll-like receptors (TLRs) are pattern recognition receptors that play a central role in the initiation and shaping of adaptive immune responses, and several TLRs have been shown to recognize mycobacterial components. In this work, we performed a case-control study to determine if common single nucleotide polymorphisms (SNPs) in genes encoding TLRs 1, 2, 4, 6, and 10 are associated with susceptibility to develop active tuberculosis in population from the state of Veracruz, Mexico. The study included 279 cases and 569 controls. The results show that the frequency of two SNPs in TLR4 was significantly higher in controls than in tuberculosis patients. The minor allele (G) of rs4986790 in TLR4 (D299G) decreased the risk of active tuberculosis in the allelic (A vs. G, OR=0.31, 95%CI=0.09‐0.81, p=0.01) and in the dominant genetic model (AA vs. GG+AG, OR=0.26, 95%CI=0.09‐0.77, p=0.02). Similarly, the minor allele (T) of rs4986791 in TLR4 (T399I) decreased the risk of active disease in the allelic model (C vs. T, OR=0.29, 95%CI=0.10‐0.90, p=0.03). We did not find an association of SNPs in TLR1 (N248S), TLR2 (R753Q), TLR6 (S249P), and TLR10 (A153S and V298I) with tuberculosis disease. These results suggest that in this population, genetic variants of TLR4 affect the susceptibility for suffering active tuberculosis disease.http://dx.doi.org/10.1155/2020/2965697 |
| spellingShingle | Enrique Ortega Sujhey Hernández-Bazán Beatriz Sánchez-Hernández Ileana Licona-Limón Javier Fuentes-Dominguez Single Nucleotide Polymorphisms in TLR4 Affect Susceptibility to Tuberculosis in Mexican Population from the State of Veracruz Journal of Immunology Research |
| title | Single Nucleotide Polymorphisms in TLR4 Affect Susceptibility to Tuberculosis in Mexican Population from the State of Veracruz |
| title_full | Single Nucleotide Polymorphisms in TLR4 Affect Susceptibility to Tuberculosis in Mexican Population from the State of Veracruz |
| title_fullStr | Single Nucleotide Polymorphisms in TLR4 Affect Susceptibility to Tuberculosis in Mexican Population from the State of Veracruz |
| title_full_unstemmed | Single Nucleotide Polymorphisms in TLR4 Affect Susceptibility to Tuberculosis in Mexican Population from the State of Veracruz |
| title_short | Single Nucleotide Polymorphisms in TLR4 Affect Susceptibility to Tuberculosis in Mexican Population from the State of Veracruz |
| title_sort | single nucleotide polymorphisms in tlr4 affect susceptibility to tuberculosis in mexican population from the state of veracruz |
| url | http://dx.doi.org/10.1155/2020/2965697 |
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