title: Polymorphisms in endothelin system genes, arsenic levels and obesity risk.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Department of Medicine, University of Valencia, Valencia, Spain; Genotyping and Genetic Diagnosis Unit, Hospital Clínico Research Foundation (INCLIVA), Valencia, Spain.
authors: Vanesa
authors: V
authors: Martínez-Barquero
authors: Genotyping and Genetic Diagnosis Unit, Hospital Clínico Research Foundation (INCLIVA), Valencia, Spain.
authors: Griselda
authors: G
authors: de Marco
authors: Department of Medicine, University of Valencia, Valencia, Spain; CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain; Service of Endocrinology and Nutrition, Hospital Clínico Universitario de Valencia, Valencia, Spain.
authors: Sergio
authors: S
authors: Martínez-Hervas
authors: Genotyping and Genetic Diagnosis Unit, Hospital Clínico Research Foundation (INCLIVA), Valencia, Spain.
authors: Pilar
authors: P
authors: Rentero
authors: Genotyping and Genetic Diagnosis Unit, Hospital Clínico Research Foundation (INCLIVA), Valencia, Spain.
authors: Inmaculada
authors: I
authors: Galan-Chilet
authors: Genotyping and Genetic Diagnosis Unit, Hospital Clínico Research Foundation (INCLIVA), Valencia, Spain.
authors: Sebastian
authors: S
authors: Blesa
authors: Internal Medicine, Rio Hortega Hospital, University of Valladolid, Valladolid, Spain.
authors: David
authors: D
authors: Morchon
authors: CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain; Service of Endocrinology and Nutrition, Hospital Regional Universitario, Málaga, Spain, Instituto de Biomedicina de Málaga (IBIMA), Málaga, Spain.
authors: Sonsoles
authors: S
authors: Morcillo
authors: CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain; Service of Endocrinology and Nutrition, Hospital Regional Universitario, Málaga, Spain, Instituto de Biomedicina de Málaga (IBIMA), Málaga, Spain.
authors: Gemma
authors: G
authors: Rojo
authors: Department of Medicine, University of Valencia, Valencia, Spain; CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain; Service of Endocrinology and Nutrition, Hospital Clínico Universitario de Valencia, Valencia, Spain.
authors: Juan Francisco
authors: JF
authors: Ascaso
authors: Department of Medicine, University of Valencia, Valencia, Spain; CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain; Service of Endocrinology and Nutrition, Hospital Clínico Universitario de Valencia, Valencia, Spain.
authors: José Tomás
authors: JT
authors: Real
authors: Internal Medicine, Rio Hortega Hospital, University of Valladolid, Valladolid, Spain.
authors: Juan Carlos
authors: JC
authors: Martín-Escudero
authors: Genotyping and Genetic Diagnosis Unit, Hospital Clínico Research Foundation (INCLIVA), Valencia, Spain; CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain.
authors: Felipe Javier
authors: FJ
authors: Chaves
mesh_terms: D001151:Arsenic / Q000097:blood*; D016232:Endothelins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D044022:Receptor, Endothelin A / Q000235:genetics*; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology
chemical_list: D016232:Endothelins; D044022:Receptor, Endothelin A; D001151:Arsenic