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Identification of HLA-DQA1 as a Susceptibility Gene for Spinal Tuberculosis by Exome Sequencing

BACKGROUND: Spinal tuberculosis (STB) is the main cause of bone and joint tuberculosis. This study aimed to screen and analyze the susceptibility genes for STB using whole-exome sequencing (WES). MATERIAL/METHODS: All exon regions of peripheral blood DNA from 6 STB patients were captured and sequenc...

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Autores principales: Shen, Jian, Shi, Shiyuan, Lai, Zhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994962/
https://www.ncbi.nlm.nih.gov/pubmed/29795056
http://dx.doi.org/10.12659/MSM.907864
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author Shen, Jian
Shi, Shiyuan
Lai, Zhen
author_facet Shen, Jian
Shi, Shiyuan
Lai, Zhen
author_sort Shen, Jian
collection PubMed
description BACKGROUND: Spinal tuberculosis (STB) is the main cause of bone and joint tuberculosis. This study aimed to screen and analyze the susceptibility genes for STB using whole-exome sequencing (WES). MATERIAL/METHODS: All exon regions of peripheral blood DNA from 6 STB patients were captured and sequenced using WES and the sequencing data were analyzed by modern bioinformatics methods to identify disease-causing mutations. Sanger sequencing was then used to validate the mutation sites in normal controls (207) and STB patients (193). The mRNA expression of the mutant gene and the serum levels of IL-6 and TNF-α were detected using qPCR or ELISA assay, respectively. RESULTS: A nonsynonymous single-nucleotide polymorphism (SNP) in the gene HLA-DQA1 (rs796778515, c.592delCinsG, CAG to GAG, p.Q198E) was identified and further validated by Sanger sequencing. The percentage of the 3 genotypes C/C, C/G and G/G in STB patients and normal controls were 37.3%, 32.1%, and 30.6% and 47.8%, 33.8%, and 18.4%, respectively. Furthermore, the C>G mutation was significantly associated with the occurrence of STB. In addition, the levels of HLA-DQA1 mRNA were significantly lower in blood cells from STB patients compared with normal controls, while the serum levels of IL-6 and TNF-α were significantly higher. CONCLUSIONS: The C>G mutation in the HLA-DQA1 gene was associated with the occurrence of STB. This variation may result in the decreased level of HLA-DQA1 mRNA and increased serum levels of IL-6 and TNF-α, which finally led the STB susceptibility.
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spelling pubmed-59949622018-06-12 Identification of HLA-DQA1 as a Susceptibility Gene for Spinal Tuberculosis by Exome Sequencing Shen, Jian Shi, Shiyuan Lai, Zhen Med Sci Monit Clinical Research BACKGROUND: Spinal tuberculosis (STB) is the main cause of bone and joint tuberculosis. This study aimed to screen and analyze the susceptibility genes for STB using whole-exome sequencing (WES). MATERIAL/METHODS: All exon regions of peripheral blood DNA from 6 STB patients were captured and sequenced using WES and the sequencing data were analyzed by modern bioinformatics methods to identify disease-causing mutations. Sanger sequencing was then used to validate the mutation sites in normal controls (207) and STB patients (193). The mRNA expression of the mutant gene and the serum levels of IL-6 and TNF-α were detected using qPCR or ELISA assay, respectively. RESULTS: A nonsynonymous single-nucleotide polymorphism (SNP) in the gene HLA-DQA1 (rs796778515, c.592delCinsG, CAG to GAG, p.Q198E) was identified and further validated by Sanger sequencing. The percentage of the 3 genotypes C/C, C/G and G/G in STB patients and normal controls were 37.3%, 32.1%, and 30.6% and 47.8%, 33.8%, and 18.4%, respectively. Furthermore, the C>G mutation was significantly associated with the occurrence of STB. In addition, the levels of HLA-DQA1 mRNA were significantly lower in blood cells from STB patients compared with normal controls, while the serum levels of IL-6 and TNF-α were significantly higher. CONCLUSIONS: The C>G mutation in the HLA-DQA1 gene was associated with the occurrence of STB. This variation may result in the decreased level of HLA-DQA1 mRNA and increased serum levels of IL-6 and TNF-α, which finally led the STB susceptibility. International Scientific Literature, Inc. 2018-05-24 /pmc/articles/PMC5994962/ /pubmed/29795056 http://dx.doi.org/10.12659/MSM.907864 Text en © Med Sci Monit, 2018 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Clinical Research
Shen, Jian
Shi, Shiyuan
Lai, Zhen
Identification of HLA-DQA1 as a Susceptibility Gene for Spinal Tuberculosis by Exome Sequencing
title Identification of HLA-DQA1 as a Susceptibility Gene for Spinal Tuberculosis by Exome Sequencing
title_full Identification of HLA-DQA1 as a Susceptibility Gene for Spinal Tuberculosis by Exome Sequencing
title_fullStr Identification of HLA-DQA1 as a Susceptibility Gene for Spinal Tuberculosis by Exome Sequencing
title_full_unstemmed Identification of HLA-DQA1 as a Susceptibility Gene for Spinal Tuberculosis by Exome Sequencing
title_short Identification of HLA-DQA1 as a Susceptibility Gene for Spinal Tuberculosis by Exome Sequencing
title_sort identification of hla-dqa1 as a susceptibility gene for spinal tuberculosis by exome sequencing
topic Clinical Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994962/
https://www.ncbi.nlm.nih.gov/pubmed/29795056
http://dx.doi.org/10.12659/MSM.907864
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