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RESEARCH PRODUCT
Polymorphisms in endothelin system genes, arsenic levels and obesity risk.
Inmaculada Galan-chiletDavid MorchonSonsoles MorcilloSergio Martínez-hervásJuan F. AscasoFelipe J. ChavesJuan Carlos Martín-escuderoGriselda De MarcoJosé T. RealVanesa Martínez-barqueroGemma RojoPilar RenteroSebastian Blesasubject
MaleEspañaObesidad: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_studyMultidisciplinary:Diseases::Pathological Conditions Signs and Symptoms::Pathologic Processes::Disease Attributes::Chronic Disease [Medical Subject Headings]Genètica humanaEndothelinsQRMiddle AgedPrognosisReceptor Endothelin APolimorfismo de nucleótido único:Anatomy::Cells::Connective Tissue Cells::Adipocytes [Medical Subject Headings]ObesitatMedicineFemaleTomografía 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 Articlemedicine.hormonemedicine.medical_specialtyGenotype:Phenomena and Processes::Mathematical Concepts::Probability::Risk [Medical Subject Headings]SciencePopulationSingle-nucleotide polymorphism:Phenomena and Processes::Metabolic Phenomena::Metabolism::Lipid Metabolism::Lipolysis [Medical Subject Headings]BiologyPolymorphism Single NucleotideArsenicReceptores de endotelinasInternal medicineAdipocitos:Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Membrane Proteins::Receptors Cell Surface::Receptors Peptide::Receptors Endothelin [Medical Subject Headings]medicineHumansGenetic Predisposition to DiseaseObesityeducation:Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism Genetic::Polymorphism Single Nucleotide [Medical Subject Headings]AdiponectinHaplotypeEnfermedad crónicamedicine.diseaseObesityEndocrinologyHaplotypesSpain:Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Adipokines::Adiponectin [Medical Subject Headings]GenotipoFollow-Up StudiesArsénicodescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-03-23 | PLoS ONE |