Martínez-Barquero, Vanesade Marco, GriseldaMartínez-Hervas, SergioRentero, PilarGalan-Chilet, InmaculadaBlesa, SebastianMorchon, DavidMorcillo, SonsolesRojo, GemmaAscaso, Juan FranciscoReal, José TomásMartín-Escudero, Juan CarlosChaves, Felipe Javier2016-08-092016-08-092015-03-23Martínez-Barquero V, de Marco G, Martínez-Hervas S, Rentero P, Galan-Chilet I, Blesa S, et al. Polymorphisms in endothelin system genes, arsenic levels and obesity risk. PLoS ONE. 2015; 10(3):e0118471http://hdl.handle.net/10668/2324BACKGROUND/OBJECTIVES:; Obesity 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/METHODS:; We 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. RESULTS:; We 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). CONCLUSIONS:; Our results support the hypothesis that polymorphisms of the EDNRB gene may influence the susceptibility to obesity and can interact with plasma arsenic levels.enAdipocitosArsénicoEnfermedad crónicaGenotipoObesidadPolimorfismo de nucleótido únicoReceptores de endotelinasEspañaTomografía computarizada por rayos XMedical Subject Headings::Anatomy::Cells::Connective Tissue Cells::AdipocytesMedical Subject Headings::Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Adipokines::AdiponectinMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Fat Distribution::AdiposityMedical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Elements::ArsenicMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Chronic DiseaseMedical Subject Headings::Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::EndothelinsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::GenotypeMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Lipid Metabolism::LipolysisMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Size::Body Weight::Overweight::ObesityMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single NucleotideMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Peptide::Receptors, EndothelinMedical Subject Headings::Phenomena and Processes::Mathematical Concepts::Probability::RiskMedical Subject Headings::Geographicals::Geographic Locations::Europe::SpainMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Image Interpretation, Computer-Assisted::Tomography, X-Ray Computedresearch article25799405open access10.1371/journal.pone.01184711932-6203PMC4370725