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Polymorphisms in endothelin system genes, arsenic levels and obesity risk

Authors :: Inmaculada Galan-Chilet
David Morchon
Sonsoles Morcillo
Sergio Martínez-Hervás
Juan F. Ascaso
Felipe J. Chaves
Juan Carlos Martín-Escudero
Griselda de Marco
José T. Real
Vanesa Martínez-Barquero
Gemma Rojo
Pilar Rentero
Sebastian Blesa
[Martínez-Barquero,V
Martínez-Hervas,S
Ascaso,JF
Real,JT] Department of Medicine, University of Valencia, Valencia, Spain. [Martínez-Barquero,V
de Marco,G
Rentero,P
Galan-Chilet,I
Blesa,S
Chaves,FJ] Genotyping and Genetic Diagnosis Unit, Hospital Clínico Research Foundation (INCLIVA), Valencia, Spain. [Martínez-Hervas,S
Morcillo,S
Rojo,G
Real,JT
Chaves,FJ] CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain. [Morcillo,S
Rojo G] Service of Endocrinology and Nutrition, Hospital Regional Universitario, Málaga, Spain, Instituto de Biomedicina de Málaga (IBIMA), Málaga, Spain. [Martínez-Hervas,S
Real, JT] Service of Endocrinology and Nutrition, Hospital Clínico Universitario de Valencia, Valencia, Spain. [Morchon,D
Martín-Escudero,JC] Internal Medicine, Rio Hortega Hospital, University of Valladolid, Valladolid, Spain.
This work was supported by the funds for research in health sciences from Carlos III Health Institute (PI07/0497 and PI11/00726), by CIBER de Diabetes y Enfermedades Metabólicas Relacionadas (CIBERDEM)
CIBERDEM is an initiative by Carlos III Health Institute in Madrid and the Spanish Health Ministry, by PROMETEO/2009/029, AP-091/11, and ACOMP/2013/039 from the Valencian Government, and by GRS 279/a/08 research project from JUNTA DE CASTILLA Y LEON Government.
Source :: PLoS ONE, Vol 10, Iss 3, p e0118471 (2015), Martinez-Vaquero, Vanesa Marco, Griselda de Martinez-Hervas, Sergio Rentero, Pilar Galan Chilet, Inmaculada Blesa, Sebastian Ascaso, Juan Francisco Morchon, David Sonsoles, Morcillo Rojo, Gemma Real, José Tomas Martin-Escudero, Juan Carlos Chaves Martínez, Felipe Javier J. 2015 Polymorphisms in endothelin system genes, arsenic levels and obesity risk Plos One 10 3 1 13, RODERIC. Repositorio Institucional de la Universitat de Valéncia, instname, PLoS ONE
Publication Year :: 2015
Publisher :: Public Library of Science (PLoS), 2015.
Abstract: Background/objectivesObesity has been linked to morbidity and mortality through increased risk for many chronic diseases. Endothelin (EDN) system has been related to endothelial function but it can be involved in lipid metabolism regulation: Receptor type A (EDNRA) activates lipolysis in adipocytes, the two endothelin receptors mediate arsenic-stimulated adipocyte dysfunction, and endothelin system can regulate adiposity by modulating adiponectin activity in different situations and, therefore, influence obesity development. The aim of the present study was to analyze if single nucleotide polymorphisms (SNPs) in the EDN system could be associated with human obesity.Subjects/methodsWe analyzed two samples of general-population-based studies from two different regions of Spain: the VALCAR Study, 468 subjects from the area of Valencia, and the Hortega Study, 1502 subjects from the area of Valladolid. Eighteen SNPs throughout five genes were analyzed using SNPlex.ResultsWe found associations for two polymorphisms of the EDNRB gene which codifies for EDN receptor type B. Genotypes AG and AA of the rs5351 were associated with a lower risk for obesity in the VALCAR sample (p=0.048, OR=0.63) and in the Hortega sample (p=0.001, OR=0.62). Moreover, in the rs3759475 polymorphism, genotypes CT and TT were also associated with lower risk for obesity in the Hortega sample (p=0.0037, OR=0.66) and in the VALCAR sample we found the same tendency (p=0.12, OR=0.70). Furthermore, upon studying the pooled population, we found a stronger association with obesity (p=0.0001, OR=0.61 and p=0.0008, OR=0.66 for rs5351 and rs3759475, respectively). Regarding plasma arsenic levels, we have found a positive association for the two SNPs studied with obesity risk in individuals with higher arsenic levels in plasma: rs5351 (p=0.0054, OR=0.51) and rs3759475 (p=0.009, OR=0.53).ConclusionsOur results support the hypothesis that polymorphisms of the EDNRB gene may influence the susceptibility to obesity and can interact with plasma arsenic levels.