Abstract
Type 2 diabetes (DM2) is an increasingly prevalent disease that challenges tuberculosis (TB) control strategies worldwide. It is significant that DM2 patients with poor glycemic control (PDM2) are prone to develo** tuberculosis. Furthermore, elucidating the molecular mechanisms that govern this susceptibility is imperative to address this problem. Therefore, a pilot transcriptomic study was performed. Human blood samples from healthy controls (CTRL, HbA1c < 6.5%), tuberculosis (TB), comorbidity TB-DM2, DM2 (HbA1c 6.5–8.9%), and PDM2 (HbA1c > 10%) groups (n = 4 each) were analyzed by differential expression using microarrays. We use a network strategy to identify potential molecular patterns linking the differentially expressed genes (DEGs) specific for TB-DM2 and PDM2 (p-value < 0.05, fold change > 2). We define OSM, PRKCD, and SOCS3 as key regulatory genes (KRGs) that modulate the immune system and related pathways. RT-qPCR assays confirmed upregulation of OSM, PRKCD, and SOCS3 genes (p < 0.05) in TB-DM2 patients (n = 18) compared to CTRL, DM2, PDM2, or TB groups (n = 17, 19, 15, and 9, respectively). Furthermore, OSM, PRKCD, and SOCS3 were associated with PDM2 susceptibility pathways toward TB-DM2 and formed a putative protein–protein interaction confirmed in STRING. Our results reveal potential molecular patterns where OSM, PRKCD, and SOCS3 are KRGs underlying the compromised immune response and susceptibility of patients with PDM2 to develop tuberculosis. Therefore, this work paved the way for fundamental research of new molecular targets in TB-DM2. Addressing their cellular implications, and the impact on the diagnosis, treatment, and clinical management of TB-DM2 could help improve the strategy to end tuberculosis for this vulnerable population.
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Data availability
The microarray files obtained here are available in the Gene Expression Omnibus (GEO) repository under the accession code GSE249102.
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Acknowledgements
We thank Jesus Núñez Contreras from Unidad de Investigación Biomédica de Zacatecas for QFT quantification and PPD determinations, as well as Gerardo Martínez Aguilar from Unidad de Investigación Biomédica Durango. We want to thanks to epidemiologist and health personnel from UIBMZ and Unidad Médica Familiar 4 (IMSS, Zacatecas), UIBM Durango, Universidad Veracruzana at Xalapa, CIAE Monterrey Nuevo Leon and Hospital General de Subzona con Medicina Familiar 41 Huatulco Oaxaca, their support for the identification of diabetes and tuberculosis patients and in the whole blood sample collection.
Funding
This work was supported by the National Council of Humanities, Sciences and Technologies [CONAHCyT], under Grant [number: A1-S-48232]; [Instituto Mexicano del Seguro Social and CONACyT] provided fellowships for graduate studies to EJS under Grant [numbers: 2017–058 and 487638], JELR under Grant [numbers: 99348716 and 389725]; and [CONACyT] to JJOV under Grant [number: 487639].
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Elena Jaime-Sánchez: Conceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Data Curation, Writing, Original draft, Visualization. Edgar E. Lara-Ramírez: Methodology, Software, Formal analysis, Data Curation, Writing—Review & Editing; Juan Ernesto López-Ramos: Investigation, Resources, Data Curation, Writing—Review & Editing. Elsy Janeth Ramos-González: Formal analysis, Resources, Data Curation, Writing—Review & Editing. Ana Laura Cisneros-Méndez: Validation, Investigation. Juan José Oropeza-Valdez: Resources, Writing—Review & Editing. Roberto Zenteno-Cuevas: Resources, Writing—Review & Editing. Gerardo Martínez-Aguilar: Resources, Writing—Review & Editing. Yadira Bastian: Resources, Writing—Review & Editing. Julio Enrique Castañeda-Delgado: Resources, Writing—Review & Editing. Carmen Judith Serrano: Review & Editing. José Antonio Enciso-Moreno: Term, Conceptualization, Methodology, Resources, Writing—Review & Editing, Supervision, Project administration, Funding acquisition.
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This study was performed in line with the principles of the Declaration of Helsinki and its later amendments. Approval was granted by the National Committee for Scientific Research and Ethics of the Instituto Mexicano del Seguro Social (IMSS) (R-2013–785-001 and R-2018–785-118).
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Jaime-Sánchez, E., Lara-Ramírez, E.E., López-Ramos, J.E. et al. Potential molecular patterns for tuberculosis susceptibility in diabetic patients with poor glycaemic control: a pilot study. Mol Genet Genomics 299, 60 (2024). https://doi.org/10.1007/s00438-024-02139-0
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DOI: https://doi.org/10.1007/s00438-024-02139-0