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

J 2014

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

KURICOVÁ, Katarína, Lukáš PÁCAL, Veronika DVOŘÁKOVÁ a Kateřina KAŇKOVÁ

Základní údaje

Originální název

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

Autoři

KURICOVÁ, Katarína (703 Slovensko, domácí), Lukáš PÁCAL (203 Česká republika, garant, domácí), Veronika DVOŘÁKOVÁ (203 Česká republika, domácí) a Kateřina KAŇKOVÁ (203 Česká republika, domácí)

Vydání

Journal of Nephrology & Therapeutics, 2014, 2161-0959

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30105 Physiology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Kód RIV

RIV/00216224:14110/14:00075467

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.4172/2161-0959.1000153

Klíčová slova anglicky

p53; Murine double minute 2 oncoprotein; Diabetic nephropathy; Cardiovascular disease; Mortality; Single nucleotide polymorphism; Association

Štítky

EL OK

Změněno: 4. 9. 2014 17:31, Ing. Mgr. Věra Pospíšilíková

Anotace

V originále

Objective: In addition to its anticancer function, p53 (regulated by murine double minute 2 oncoprotein, MDM2) has recently been shown to control intracellular metabolic processes. It participates in the regulation of glucose, fatty and amino acid and purine metabolism, influences mitochondrial integrity and oxidative phosphorylation, insulin sensitivity, antioxidant response and autophagy. With respect to the possible impact of genetic variability in p53 and MDM2 on metabolic compensation the aim of the study was to analyse the effect of common germ line Single Nucleotide Polymorphisms (SNPs) - Arg72Pro in the TP53 and SNP309 in the MDM2 - on the progression of Diabetic Nephropathy (DN), cardiovascular morbidity and mortality and all-cause mortality in Type 2 Diabetes Mellitus (T2DM) subjects. Methods: The cross-sectional study comprised a total of 309 (a sum of 155 and 154) unrelated Caucasian diabetic patients with diabetes duration at least 10 years and variable renal function at baseline (309, mean age was 67.2 +/- 10.8 years). The stage of diabetic nephropathy was defined according to the urinary albumin excretion and glomerular filtration rate. Patients were followed-up for median 37 (20-59) months. The following end-points were considered: (a) progression of DN, (b) major cardiovascular event (non-fatal or fatal myocardial infarction or stroke, limb amputation, revascularization), (c) all-cause mortality. Genotypes were determined by PCR-based methodology. Time-to-event analysis using Kaplan-Meier curves and log-rank test was used. Results: We found significant difference between CG+GG vs. CC genotypes of the p53 Arg72Pro SNP for DN progression (P=0.046, log-rank test). Carriers of genotypes containing G allele (previously associated with susceptibility to T2DM) had faster progression of DN than CC genotype carriers. We did not find any significant difference between genotypes of MDM2 SNP for any of the end-points studied. Conclusions: Presented findings in general support the role of p53 in the pathogenesis of metabolic diseases, namely progression of hyperglycemia-related morbidity. Nevertheless, further studies are warranted to elucidate the eventual causal involvement of p53 pathway in the development of diabetic complications.

Citovat

KURICOVÁ, Katarína, Lukáš PÁCAL, Veronika DVOŘÁKOVÁ a Kateřina KAŇKOVÁ. Association of the Arg72Pro Polymorphism in p53 with Progression of Diabetic Nephropathy in T2DM Subjects. Journal of Nephrology & Therapeutics. 2014, roč. 4, č. 2, s. 1-3. ISSN 2161-0959. Dostupné z: https://dx.doi.org/10.4172/2161-0959.1000153.

@article{1182600,
   author = {Kuricová, Katarína and Pácal, Lukáš and Dvořáková, Veronika and Kaňková, Kateřina},
   article_number = {2},
   doi = {http://dx.doi.org/10.4172/2161-0959.1000153},
   keywords = {p53; Murine double minute 2 oncoprotein; Diabetic nephropathy; Cardiovascular disease; Mortality; Single nucleotide polymorphism; Association},
   language = {eng},
   issn = {2161-0959},
   journal = {Journal of Nephrology & Therapeutics},
   title = {Association of the Arg72Pro Polymorphism in p53 with Progression of Diabetic Nephropathy in T2DM Subjects},
   url = {http://omicsonline.org/open-access/association-of-the-argpro-polymorphism-in-p-with-progression-of-diabetic-nephropathy-in-tdm-subjects-2161-0959.1000153.pdf},
   volume = {4},
   year = {2014}
}

TY  - JOUR
ID  - 1182600
AU  - Kuricová, Katarína - Pácal, Lukáš - Dvořáková, Veronika - Kaňková, Kateřina
PY  - 2014
TI  - Association of the Arg72Pro Polymorphism in p53 with Progression of Diabetic Nephropathy in T2DM Subjects
JF  - Journal of Nephrology & Therapeutics
VL  - 4
IS  - 2
SP  - 1-3
EP  - 1-3
SN  - 21610959
KW  - p53
KW  - Murine double minute 2 oncoprotein
KW  - Diabetic nephropathy
KW  - Cardiovascular disease
KW  - Mortality
KW  - Single nucleotide polymorphism
KW  - Association
UR  - http://omicsonline.org/open-access/association-of-the-argpro-polymorphism-in-p-with-progression-of-diabetic-nephropathy-in-tdm-subjects-2161-0959.1000153.pdf
N2  - Objective: In addition to its anticancer function, p53 (regulated by murine double minute 2 oncoprotein, MDM2) has recently been shown to control intracellular metabolic processes. It participates in the regulation of glucose, fatty and amino acid and purine metabolism, influences mitochondrial integrity and oxidative phosphorylation, insulin sensitivity, antioxidant response and autophagy. With respect to the possible impact of genetic variability in p53 and MDM2 on metabolic compensation the aim of the study was to analyse the effect of common germ line Single Nucleotide Polymorphisms (SNPs) - Arg72Pro in the TP53 and SNP309 in the MDM2 - on the progression of Diabetic Nephropathy (DN), cardiovascular morbidity and mortality and all-cause mortality in Type 2 Diabetes Mellitus (T2DM) subjects. Methods: The cross-sectional study comprised a total of 309 (a sum of 155 and 154) unrelated Caucasian diabetic patients with diabetes duration at least 10 years and variable renal function at baseline (309, mean age was 67.2 +/- 10.8 years). The stage of diabetic nephropathy was defined according to the urinary albumin excretion and glomerular filtration rate. Patients were followed-up for median 37 (20-59) months. The following end-points were considered: (a) progression of DN, (b) major cardiovascular event (non-fatal or fatal myocardial infarction or stroke, limb amputation, revascularization), (c) all-cause mortality. Genotypes were determined by PCR-based methodology. Time-to-event analysis using Kaplan-Meier curves and log-rank test was used. Results: We found significant difference between CG+GG vs. CC genotypes of the p53 Arg72Pro SNP for DN progression (P=0.046, log-rank test). Carriers of genotypes containing G allele (previously associated with susceptibility to T2DM) had faster progression of DN than CC genotype carriers. We did not find any significant difference between genotypes of MDM2 SNP for any of the end-points studied. Conclusions: Presented findings in general support the role of p53 in the pathogenesis of metabolic diseases, namely progression of hyperglycemia-related morbidity. Nevertheless, further studies are warranted to elucidate the eventual causal involvement of p53 pathway in the development of diabetic complications.
ER  -

KURICOVÁ, Katarína, Lukáš PÁCAL, Veronika DVOŘÁKOVÁ a Kateřina KAŇKOVÁ. Association of the Arg72Pro Polymorphism in p53 with Progression of Diabetic Nephropathy in T2DM Subjects. \textit{Journal of Nephrology \&{} Therapeutics}. 2014, roč.~4, č.~2, s.~1-3. ISSN~2161-0959. Dostupné z: https://dx.doi.org/10.4172/2161-0959.1000153.

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