24 May 2018 : Clinical Research
Identification of HLA-DQA1 as a Susceptibility Gene for Spinal Tuberculosis by Exome Sequencing
Jian Shen1ACEG*, Shiyuan Shi1BDF, Zhen Lai1BCDDOI: 10.12659/MSM.907864
Med Sci Monit 2018; 24: CLR3442-3449
Abstract
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 AND 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.
Keywords: High-Throughput Nucleotide Sequencing
Editorial
01 May 2024 : Editorial
Editorial: First Regulatory Approval for Adoptive Cell Therapy with Autologous Tumor-Infiltrating Lymphocytes (TILs) – Lifileucel (Amtagvi)DOI: 10.12659/MSM.944927
Med Sci Monit 2024; 30:e944927
In Press
12 Mar 2024 : Clinical Research
Metabolomic Alterations in Methotrexate Treatment of Moderate-to-Severe PsoriasisMed Sci Monit In Press; DOI: 10.12659/MSM.943360
14 Mar 2024 : Clinical Research
Renal Dysfunction Increases Risk of Adverse Cardiovascular Events in 5-Year Follow-Up Study of Intermediate...Med Sci Monit In Press; DOI: 10.12659/MSM.943956
15 Mar 2024 : Clinical Research
Impact of One-Lung Ventilation on Oxygenation and Ventilation Time in Thoracoscopic Heart Surgery: A Compar...Med Sci Monit In Press; DOI: 10.12659/MSM.943089
14 Mar 2024 : Clinical Research
Differential DHA and EPA Levels in Women with Preterm and Term Births: A Tertiary Hospital Study in IndonesiaMed Sci Monit In Press; DOI: 10.12659/MSM.943895
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952