Transcriptional Profiling and Biological Pathway(s) Analysis of Type 2 Diabetes Mellitus in a Pakistani Population

Zarish Noreen, Christopher A. Loffredo, Attya Bhatti, Jyothirmai J. Simhadri, Gail Nunlee-Bland, Thomas Nnanabu, Peter John, Jahangir S. Khan and Somiranjan Ghosh
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Zarish Noreen: HealthCare Biotechnology, Atta-Ur-Rahman School of Applied Biosciences, National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan
Christopher A. Loffredo: Departments of Oncology and of Biostatistics, Georgetown University, Washington, DC 20057, USA
Attya Bhatti: HealthCare Biotechnology, Atta-Ur-Rahman School of Applied Biosciences, National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan
Jyothirmai J. Simhadri: Department of Pediatrics and Child Health, College of Medicine, Howard University, Washington, DC 20059, USA
Gail Nunlee-Bland: Department of Pediatrics and Child Health, College of Medicine, Howard University, Washington, DC 20059, USA
Thomas Nnanabu: Department of Biology, Howard University, Washington, DC 20059, USA
Peter John: HealthCare Biotechnology, Atta-Ur-Rahman School of Applied Biosciences, National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan
Jahangir S. Khan: Department of Surgery, Rawalpindi Medical College, Rawalpindi, Punjab 46000, Pakistan
Somiranjan Ghosh: Department of Pediatrics and Child Health, College of Medicine, Howard University, Washington, DC 20059, USA

IJERPH, 2020, vol. 17, issue 16, 1-20

Abstract: The epidemic of type 2 diabetes mellitus (T2DM) is an important global health concern. Our earlier epidemiological investigation in Pakistan prompted us to conduct a molecular investigation to decipher the differential genetic pathways of this health condition in relation to non-diabetic controls. Our microarray studies of global gene expression were conducted on the Affymetrix platform using Human Genome U133 Plus 2.0 Array along with Ingenuity Pathway Analysis ( IPA ) to associate the affected genes with their canonical pathways. High-throughput qRT-PCR TaqMan Low Density Array (TLDA) was performed to validate the selected differentially expressed genes of our interest, viz., ARNT, LEPR, MYC, RRAD, CYP2D6 , TP53, APOC1, APOC2, CYP1B1, SLC2A13, and SLC33A1 using a small population validation sample (n = 15 cases and their corresponding matched controls). Overall, our small pilot study revealed a discrete gene expression profile in cases compared to controls. The disease pathways included: Insulin Receptor Signaling , Type II Diabetes Mellitus Signaling, Apoptosis Signaling , Aryl Hydrocarbon Receptor Signaling , p53 Signaling , Mitochondrial Dysfunction, Chronic Myeloid Leukemia Signaling , Parkinson’s Signaling, Molecular Mechanism of Cancer, and Cell Cycle G1/S Checkpoint Regulation, GABA Receptor Signaling, Neuroinflammation Signaling Pathway, Dopamine Receptor Signaling, Sirtuin Signaling Pathway , Oxidative Phosphorylation , LXR/RXR Activation , and Mitochondrial Dysfunction, strongly consistent with the evidence from epidemiological studies. These gene fingerprints could lead to the development of biomarkers for the identification of subgroups at high risk for future disease well ahead of time, before the actual disease becomes visible.

Keywords: type 2 diabetes; Pakistan; gene expression; disease pathways; gene validation; biomarkers (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2020
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