1. Polymorphisms in endothelin system genes, arsenic levels and obesity risk
- Author
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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), and 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.
- Subjects
Male ,España ,Obesidad ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Fat Distribution::Adiposity [Medical Subject Headings] ,Endothelins ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Endothelins [Medical Subject Headings] ,Polymorphism (computer science) ,Risk Factors ,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::Obesity [Medical Subject Headings] ,Chemicals and Drugs::Inorganic Chemicals::Elements::Arsenic [Medical Subject Headings] ,Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings] ,education.field_of_study ,Multidisciplinary ,Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Chronic Disease [Medical Subject Headings] ,Genètica humana ,Middle Aged ,Prognosis ,Receptor, Endothelin A ,Polimorfismo de nucleótido único ,Anatomy::Cells::Connective Tissue Cells::Adipocytes [Medical Subject Headings] ,Obesitat ,Medicine ,Female ,Tomografía computarizada por rayos X ,Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings] ,Endothelin receptor ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Image Interpretation, Computer-Assisted::Tomography, X-Ray Computed [Medical Subject Headings] ,Research Article ,medicine.hormone ,medicine.medical_specialty ,Genotype ,Phenomena and Processes::Mathematical Concepts::Probability::Risk [Medical Subject Headings] ,Science ,Population ,Single-nucleotide polymorphism ,Phenomena and Processes::Metabolic Phenomena::Metabolism::Lipid Metabolism::Lipolysis [Medical Subject Headings] ,Biology ,Polymorphism, Single Nucleotide ,Arsenic ,Receptores de endotelinas ,Internal medicine ,Adipocitos ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Peptide::Receptors, Endothelin [Medical Subject Headings] ,medicine ,Humans ,Genetic Predisposition to Disease ,Obesity ,education ,Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings] ,Adiponectin ,Haplotype ,Enfermedad crónica ,medicine.disease ,Endocrinology ,Haplotypes ,Spain ,Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Adipokines::Adiponectin [Medical Subject Headings] ,Genotipo ,Follow-Up Studies ,Arsénico - 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.
- Published
- 2015