In silico identification and functional prediction of differentially expressed genes in South Asian populations associated with type 2 diabetes

Md Golam Rabby; Md Hafizur Rahman; Md Numan Islam; Md Mostafa Kamal; Mrityunjoy Biswas; Mantasa Bonny; Md Mahmudul Hasan

doi:10.1371/journal.pone.0294399

In silico identification and functional prediction of differentially expressed genes in South Asian populations associated with type 2 diabetes

PLoS One. 2023 Dec 14;18(12):e0294399. doi: 10.1371/journal.pone.0294399. eCollection 2023.

Authors

Md Golam Rabby¹, Md Hafizur Rahman^{2

3}, Md Numan Islam¹, Md Mostafa Kamal¹, Mrityunjoy Biswas², Mantasa Bonny¹, Md Mahmudul Hasan¹

Affiliations

¹ Department of Nutrition and Food Technology, Jashore University of Science and Technology, Khulna, Bangladesh.
² Department of Agro Product Processing Technology, Jashore University of Science and Technology, Khulna, Bangladesh.
³ Faculty of Food Sciences and Safety, Department of Quality Control and Safety Management, Khulna Agricultural University, Khulna, Bangladesh.

Abstract

Type 2 diabetes (T2D) is one of the major metabolic disorders in humans caused by hyperglycemia and insulin resistance syndrome. Although significant genetic effects on T2D pathogenesis are experimentally proved, the molecular mechanism of T2D in South Asian Populations (SAPs) is still limited. Hence, the current research analyzed two Gene Expression Omnibus (GEO) and 17 Genome-Wide Association Studies (GWAS) datasets associated with T2D in SAP to identify DEGs (differentially expressed genes). The identified DEGs were further analyzed to explore the molecular mechanism of T2D pathogenesis following a series of bioinformatics approaches. Following PPI (Protein-Protein Interaction), 867 potential DEGs and nine hub genes were identified that might play significant roles in T2D pathogenesis. Interestingly, CTNNB1 and RUNX2 hub genes were found to be unique for T2D pathogenesis in SAPs. Then, the GO (Gene Ontology) showed the potential biological, molecular, and cellular functions of the DEGs. The target genes also interacted with different pathways of T2D pathogenesis. In fact, 118 genes (including HNF1A and TCF7L2 hub genes) were directly associated with T2D pathogenesis. Indeed, eight key miRNAs among 2582 significantly interacted with the target genes. Even 64 genes were downregulated by 367 FDA-approved drugs. Interestingly, 11 genes showed a wide range (9-43) of drug specificity. Hence, the identified DEGs may guide to elucidate the molecular mechanism of T2D pathogenesis in SAPs. Therefore, integrating the research findings of the potential roles of DEGs and candidate drug-mediated downregulation of marker genes, future drugs or treatments could be developed to treat T2D in SAPs.

Copyright: © 2023 Rabby et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

MeSH terms

Computational Biology
Diabetes Mellitus, Type 2* / genetics
Gene Expression Profiling
Genome-Wide Association Study
Humans
MicroRNAs* / genetics
MicroRNAs* / metabolism

Substances

MicroRNAs

Grants and funding

The research work was done with the financial support from ICT division, Ministry of Posts, Telecommunications and Information Technology, Government of the People's Republic of Bangladesh. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.