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AMPD1 gene mutations are associated with obesity and diabetes in Polish patients with cardiovascular diseases

Previous studies showed an association of the common functional polymorphism (C34T, Gln12Stop) in the adenosine monophosphate deaminase-1 (AMPD1) gene with survival in heart failure (HF) and/or coronary artery disease (CAD). The aim of the study was to search for other mutations in selected regions...

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Autores principales: Safranow, Krzysztof, Suchy, Janina, Jakubowska, Katarzyna, Olszewska, Maria, Bińczak-Kuleta, Agnieszka, Kurzawski, Grzegorz, Rzeuski, Ryszard, Czyżycka, Edyta, Łoniewska, Beata, Kornacewicz-Jach, Zdzisława, Ciechanowicz, Andrzej, Chlubek, Dariusz
Formato: Texto
Lenguaje:English
Publicado: Springer-Verlag 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026686/
https://www.ncbi.nlm.nih.gov/pubmed/21108053
http://dx.doi.org/10.1007/s13353-010-0009-x
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author Safranow, Krzysztof
Suchy, Janina
Jakubowska, Katarzyna
Olszewska, Maria
Bińczak-Kuleta, Agnieszka
Kurzawski, Grzegorz
Rzeuski, Ryszard
Czyżycka, Edyta
Łoniewska, Beata
Kornacewicz-Jach, Zdzisława
Ciechanowicz, Andrzej
Chlubek, Dariusz
author_facet Safranow, Krzysztof
Suchy, Janina
Jakubowska, Katarzyna
Olszewska, Maria
Bińczak-Kuleta, Agnieszka
Kurzawski, Grzegorz
Rzeuski, Ryszard
Czyżycka, Edyta
Łoniewska, Beata
Kornacewicz-Jach, Zdzisława
Ciechanowicz, Andrzej
Chlubek, Dariusz
author_sort Safranow, Krzysztof
collection PubMed
description Previous studies showed an association of the common functional polymorphism (C34T, Gln12Stop) in the adenosine monophosphate deaminase-1 (AMPD1) gene with survival in heart failure (HF) and/or coronary artery disease (CAD). The aim of the study was to search for other mutations in selected regions of the AMPD1 gene in Polish CAD and HF patients, and to analyze their associations with obesity and diabetes. Exons 2, 3, 5, and 7 of AMPD1 were scanned for mutations in 97 patients with CAD without HF (CAD+ HF−), 104 patients with HF (HF+), and 200 newborns from North-Western Poland using denaturing high-performance liquid chromatography (DHPLC), polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP), and direct sequencing. Frequencies of AMPD1 C34T mutation, as well as novel A99G, G512A, IVS4-6delT, and C784T sequence alterations, were similar in the three groups, but 860T mutated allele was less frequent in the combined CAD+ HF− and HF+ groups than in the controls (1.7% vs. 4.3%, p = 0.040). Heterozygous 34CT genotype was associated with lower (odds ratio [OR] = 0.32, 95% confidence interval [CI] = 0.13–0.81) and 860AT with higher (OR = 13.7, 95%CI = 1.6–118) prevalence of diabetes or hyperglycemia in relation to wild-type homozygotes. Abdominal obesity was more frequent in 860AT patients than in wild-type homozygotes and 34CT heterozygotes (86% vs. 40% vs. 29%, p < 0.05). Nine genes containing polymorphisms linked with AMPD1 C34T mutation were found in the HapMap database. AMPD1 C34T nonsense mutation is associated with reduced prevalence of diabetes and obesity in patients with CAD or HF, but A860T substitution seems to exert opposite metabolic effects and should always be accounted for in the studies of the AMPD1 genotype.
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spelling pubmed-30266862011-02-22 AMPD1 gene mutations are associated with obesity and diabetes in Polish patients with cardiovascular diseases Safranow, Krzysztof Suchy, Janina Jakubowska, Katarzyna Olszewska, Maria Bińczak-Kuleta, Agnieszka Kurzawski, Grzegorz Rzeuski, Ryszard Czyżycka, Edyta Łoniewska, Beata Kornacewicz-Jach, Zdzisława Ciechanowicz, Andrzej Chlubek, Dariusz J Appl Genet Human genetics · Short Communication Previous studies showed an association of the common functional polymorphism (C34T, Gln12Stop) in the adenosine monophosphate deaminase-1 (AMPD1) gene with survival in heart failure (HF) and/or coronary artery disease (CAD). The aim of the study was to search for other mutations in selected regions of the AMPD1 gene in Polish CAD and HF patients, and to analyze their associations with obesity and diabetes. Exons 2, 3, 5, and 7 of AMPD1 were scanned for mutations in 97 patients with CAD without HF (CAD+ HF−), 104 patients with HF (HF+), and 200 newborns from North-Western Poland using denaturing high-performance liquid chromatography (DHPLC), polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP), and direct sequencing. Frequencies of AMPD1 C34T mutation, as well as novel A99G, G512A, IVS4-6delT, and C784T sequence alterations, were similar in the three groups, but 860T mutated allele was less frequent in the combined CAD+ HF− and HF+ groups than in the controls (1.7% vs. 4.3%, p = 0.040). Heterozygous 34CT genotype was associated with lower (odds ratio [OR] = 0.32, 95% confidence interval [CI] = 0.13–0.81) and 860AT with higher (OR = 13.7, 95%CI = 1.6–118) prevalence of diabetes or hyperglycemia in relation to wild-type homozygotes. Abdominal obesity was more frequent in 860AT patients than in wild-type homozygotes and 34CT heterozygotes (86% vs. 40% vs. 29%, p < 0.05). Nine genes containing polymorphisms linked with AMPD1 C34T mutation were found in the HapMap database. AMPD1 C34T nonsense mutation is associated with reduced prevalence of diabetes and obesity in patients with CAD or HF, but A860T substitution seems to exert opposite metabolic effects and should always be accounted for in the studies of the AMPD1 genotype. Springer-Verlag 2010-11-25 2011 /pmc/articles/PMC3026686/ /pubmed/21108053 http://dx.doi.org/10.1007/s13353-010-0009-x Text en © The Author(s) 2010 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Human genetics · Short Communication
Safranow, Krzysztof
Suchy, Janina
Jakubowska, Katarzyna
Olszewska, Maria
Bińczak-Kuleta, Agnieszka
Kurzawski, Grzegorz
Rzeuski, Ryszard
Czyżycka, Edyta
Łoniewska, Beata
Kornacewicz-Jach, Zdzisława
Ciechanowicz, Andrzej
Chlubek, Dariusz
AMPD1 gene mutations are associated with obesity and diabetes in Polish patients with cardiovascular diseases
title AMPD1 gene mutations are associated with obesity and diabetes in Polish patients with cardiovascular diseases
title_full AMPD1 gene mutations are associated with obesity and diabetes in Polish patients with cardiovascular diseases
title_fullStr AMPD1 gene mutations are associated with obesity and diabetes in Polish patients with cardiovascular diseases
title_full_unstemmed AMPD1 gene mutations are associated with obesity and diabetes in Polish patients with cardiovascular diseases
title_short AMPD1 gene mutations are associated with obesity and diabetes in Polish patients with cardiovascular diseases
title_sort ampd1 gene mutations are associated with obesity and diabetes in polish patients with cardiovascular diseases
topic Human genetics · Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026686/
https://www.ncbi.nlm.nih.gov/pubmed/21108053
http://dx.doi.org/10.1007/s13353-010-0009-x
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