PMID- 32823525
OWN - NLM
STAT- MEDLINE
DCOM- 20201204
LR  - 20230301
IS  - 1660-4601 (Electronic)
IS  - 1661-7827 (Print)
IS  - 1660-4601 (Linking)
VI  - 17
IP  - 16
DP  - 2020 Aug 13
TI  - Transcriptional Profiling and Biological Pathway(s) Analysis of Type 2 Diabetes 
      Mellitus in a Pakistani Population.
LID - 10.3390/ijerph17165866 [doi]
LID - 5866
AB  - 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.
FAU - Noreen, Zarish
AU  - Noreen Z
AD  - HealthCare Biotechnology, Atta-Ur-Rahman School of Applied Biosciences, National 
      University of Sciences and Technology (NUST), Islamabad 44000, Pakistan.
FAU - Loffredo, Christopher A
AU  - Loffredo CA
AD  - Departments of Oncology and of Biostatistics, Georgetown University, Washington, 
      DC 20057, USA.
FAU - Bhatti, Attya
AU  - Bhatti A
AD  - HealthCare Biotechnology, Atta-Ur-Rahman School of Applied Biosciences, National 
      University of Sciences and Technology (NUST), Islamabad 44000, Pakistan.
FAU - Simhadri, Jyothirmai J
AU  - Simhadri JJ
AD  - Department of Pediatrics and Child Health, College of Medicine, Howard 
      University, Washington, DC 20059, USA.
FAU - Nunlee-Bland, Gail
AU  - Nunlee-Bland G
AUID- ORCID: 0000-0001-6388-688X
AD  - Department of Pediatrics and Child Health, College of Medicine, Howard 
      University, Washington, DC 20059, USA.
FAU - Nnanabu, Thomas
AU  - Nnanabu T
AD  - Department of Biology, Howard University, Washington, DC 20059, USA.
FAU - John, Peter
AU  - John P
AD  - HealthCare Biotechnology, Atta-Ur-Rahman School of Applied Biosciences, National 
      University of Sciences and Technology (NUST), Islamabad 44000, Pakistan.
FAU - Khan, Jahangir S
AU  - Khan JS
AD  - Department of Surgery, Rawalpindi Medical College, Rawalpindi, Punjab 46000, 
      Pakistan.
FAU - Ghosh, Somiranjan
AU  - Ghosh S
AUID- ORCID: 0000-0002-5280-7418
AD  - Department of Pediatrics and Child Health, College of Medicine, Howard 
      University, Washington, DC 20059, USA.
AD  - Department of Biology, Howard University, Washington, DC 20059, USA.
LA  - eng
GR  - U54 MD007597/MD/NIMHD NIH HHS/United States
GR  - 2-U54 MD00759731/MD/NIMHD NIH HHS/United States
GR  - 1-P20 CA262617-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200813
PL  - Switzerland
TA  - Int J Environ Res Public Health
JT  - International journal of environmental research and public health
JID - 101238455
RN  - 0 (Glucose Transport Proteins, Facilitative)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - *Diabetes Mellitus, Type 2/epidemiology/genetics
MH  - *Gene Expression Profiling
MH  - Glucose Transport Proteins, Facilitative
MH  - Humans
MH  - Pakistan/epidemiology
MH  - Pilot Projects
MH  - Transcriptome
MH  - ras Proteins
PMC - PMC7460550
OTO - NOTNLM
OT  - Pakistan
OT  - biomarkers
OT  - disease pathways
OT  - gene expression
OT  - gene validation
OT  - type 2 diabetes
COIS- The authors declare no conflicts of interest.
EDAT- 2020/08/23 06:00
MHDA- 2020/12/15 06:00
PMCR- 2020/08/01
CRDT- 2020/08/23 06:00
PHST- 2020/06/25 00:00 [received]
PHST- 2020/08/03 00:00 [revised]
PHST- 2020/08/06 00:00 [accepted]
PHST- 2020/08/23 06:00 [entrez]
PHST- 2020/08/23 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/08/01 00:00 [pmc-release]
AID - ijerph17165866 [pii]
AID - ijerph-17-05866 [pii]
AID - 10.3390/ijerph17165866 [doi]
PST - epublish
SO  - Int J Environ Res Public Health. 2020 Aug 13;17(16):5866. doi: 
      10.3390/ijerph17165866.