Association of the Arg72Pro Polymorphism in p53 with Progression of Diabetic Nephropathy in T2DM Subjects

Kuricová, Katarína; Pácal, Lukáš; Dvořáková, Veronika; Kaňková, Kateřina

doi:10.4172/2161-0959.1000153

Cited by 4 publications

(1 citation statement)

References 19 publications

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“…In our study, this gene was downregulated in nearly all the patients with T2DM, as has been noted in some prior studies [90,91]. TP53 is also involved in glucose regulation, mitochondrial integrity, fatty acid metabolism, and antioxidant mechanisms [92]. It also regulates the expression of genes including glucose transporter genes Glut 1 and Glut 4 as well as the genes involved in cellular mechanism and glucose homeostasis [93].…”

Section: Altered Pathways In T2dmsupporting

confidence: 84%

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

Noreen

Loffredo

Bhatti

et al. 2020

IJERPH

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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.

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Section: Altered Pathways In T2dmsupporting

confidence: 84%

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

Noreen

Loffredo

Bhatti

et al. 2020

IJERPH

View full text Add to dashboard Cite

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Is p53 Involved in Tissue‐Specific Insulin Resistance Formation?

Strycharz

Drzewoski

Szemraj

et al. 2017

Oxidative Medicine and Cellular Longevity

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p53 constitutes an extremely versatile molecule, primarily involved in sensing the variety of cellular stresses. Functional p53 utilizes a plethora of mechanisms to protect cell from deleterious repercussions of genotoxic insults, where senescence deserves special attention. While the impressive amount of p53 roles has been perceived solely by the prism of antioncogenic effect, its presence seems to be vastly connected with metabolic abnormalities underlain by cellular aging, obesity, and inflammation. p53 has been found to regulate multiple biochemical processes such as glycolysis, oxidative phosphorylation, lipolysis, lipogenesis, β-oxidation, gluconeogenesis, and glycogen synthesis. Notably, p53-mediated metabolic effects are totally up to results of insulin action. Accumulating amount of data identifies p53 to be a factor activated upon hyperglycemia or excessive calorie intake, thus contributing to low-grade chronic inflammation and systemic insulin resistance. Prominent signs of its actions have been observed in muscles, liver, pancreas, and adipose tissue being associated with attenuation of insulin signalling. p53 is of crucial importance for the regulation of white and brown adipogenesis simultaneously being a repressor for preadipocyte differentiation. This review provides a profound insight into p53-dependent metabolic actions directed towards promotion of insulin resistance as well as presenting experimental data regarding obesity-induced p53-mediated metabolic abnormalities.

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TP53 Pro72 Allele Is Enriched in Oral Tongue Cancer and Frequently Mutated in Esophageal Cancer in India

et al. 2014

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PurposeThe tumor suppressor p53 is known to be inactivated frequently in various cancers. In addition, germline polymorphisms in TP53 are known to affect protein function and influence risk of developing different types of cancers. In this study, we analyzed the association of TP53 Pro72Arg polymorphism with squamous cell carcinoma of oral tongue (SCCOT) and esophagus (ESCC) in India.MethodsWe assessed the distribution of TP53 Pro72Arg polymorphism in one hundred and fifteen and eighty two SCCOT and ESCC patients, respectively, with respect to one hundred and ten healthy controls from the same population. In addition, we analyzed association of the polymorphism with several clinico-pathological and molecular parameters.ResultsPro72 allele was significantly enriched in SCCOT patients compared to the healthy control group but neither allele was enriched in ESCC. Interestingly, Pro72 allele was preferentially mutated in ESCC which was confirmed by analysis of samples heterozygous for Pro72Arg.ConclusionsOur study revealed the association of Pro72 allele with SCCOT suggesting the effect of this polymorphism on SCCOT risk. Preferential mutation of Pro72 allele exclusively in ESCC indicates the need for further studies to understand the tissue specific effect of p53 polymorphism.

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Association of the Arg72Pro Polymorphism in p53 with Progression of Diabetic Nephropathy in T2DM Subjects

Cited by 4 publications

References 19 publications

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

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

Is p53 Involved in Tissue‐Specific Insulin Resistance Formation?

TP53 Pro72 Allele Is Enriched in Oral Tongue Cancer and Frequently Mutated in Esophageal Cancer in India

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