Polymorphisms in endothelin system genes, arsenic levels and obesity risk

PLoS One. 2015 Mar 23;10(3):e0118471. doi: 10.1371/journal.pone.0118471. eCollection 2015.

Abstract

Background/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arsenic / blood*
  • Endothelins / genetics*
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / epidemiology*
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Receptor, Endothelin A / genetics*
  • Risk Factors
  • Spain / epidemiology

Substances

  • Endothelins
  • Receptor, Endothelin A
  • Arsenic

Grants and funding

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. V. Martínez-Barquero is granted by Spanish Ministry of Education, Social Politics and Sport with the "Formación del Profesorado Universitario" Program (AP2010-4754). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.