Association Between Promoter Methylation of Vitamin D Metabolic Pathway Genes and Tuberculosis and Diabetes Comorbidity in a Chinese Han Population: A Case–Control Study

Yong, Chen; Peng, Anzhou; Li, Kun; Liu, Lei; Zhang, Fazhen; Chen, Jin; Zhang, Huifen; Li, Linyang; Yang, Hailin; Xu, Xiuli; Zhang, Qiu

doi:10.2147/jir.s393224

Cited by 1 publication

(1 citation statement)

References 32 publications

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“…However, limited efforts have been made in advancing diagnostic markers for tuberculosis. Research suggests that abnormal methylation in the promoter regions of TLR2 or genes related to vitamin D metabolism in peripheral blood is associated with tuberculosis risk (Chen et al, 2014;Wang et al, 2018;Chen et al, 2022b). Furthermore, two differentially methylated regions (DMRs), chr3: 195635643-195636243 and chr6: 29691631-29692475, exhibit an AUC of 0.838, sensitivity of 0.645, and specificity of 0.903 in TB and HC (Lyu et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Exploring TSPAN4 promoter methylation as a diagnostic biomarker for tuberculosis

Zhang,

Chen,

Zhang

et al. 2024

Front. Genet.

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Background:Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a persistent infectious disease threatening human health. The existing diagnostic methods still have significant shortcomings, including a low positivity rate in pathogen-based diagnoses and the inability of immunological diagnostics to detect active TB. Hence, it is urgent to develop new techniques to detect TB more accurate and earlier. This research aims to scrutinize and authenticate DNA methylation markers suitable for tuberculosis diagnosis. Concurrently, Providing a new approach for tuberculosis diagnosis.Methods:Blood samples from patients with newly diagnosed tuberculosis and healthy controls (HC) were utilized in this study. Examining methylation microarray data from 40 whole blood samples (22TB + 18HC), we employed two procedures: signature gene methylated position analysis and signature region methylated position analysis to pinpoint distinctive methylated positions. Based on the screening results, diagnostic classifiers are constructed through machine learning, and validation was conducted through pyrosequencing in a separate queue (22TB + 18HC). Culminating in the development of a new tuberculosis diagnostic method via quantitative real-time methylation specific PCR (qMSP).Results:The combination of the two procedures revealed a total of 10 methylated positions, all of which were located in the promoter region. These 10 signature methylated positions facilitated the construction of a diagnostic classifier, exhibiting robust diagnostic accuracy in both cross-validation and external test sets. The LDA model demonstrated the best classification performance, achieving an AUC of 0.83, specificity of 0.8, and sensitivity of 0.86 on the external test set. Furthermore, the validation of signature methylated positions through pyrosequencing demonstrated high agreement with screening outcomes. Additionally, qMSP detection of 2 potential hypomethylated positions (cg04552852 and cg12464638) exhibited promising results, yielding an AUC of 0.794, specificity of 0.720, and sensitivity of 0.816.Conclusion:Our study demonstrates that the validated signature methylated positions through pyrosequencing emerge as plausible biomarkers for tuberculosis diagnosis. The specific methylation markers in the TSPAN4 gene, identified in whole blood samples, hold promise for improving tuberculosis diagnosis. This approach could significantly enhance diagnostic accuracy and speed, offering a new avenue for early detection and treatment.

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