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

Polymorphisms in endothelin system genes, arsenic levels and obesity risk

Vanesa Martínez-Barquero  1 , Griselda de Marco  2 , Sergio Martínez-Hervas  3 , Pilar Rentero  2 , Inmaculada Galan-Chilet  2 , Sebastian Blesa  2 , David Morchon  4 , Sonsoles Morcillo  5 , Gemma Rojo  5 , Juan Francisco Ascaso  3 , José Tomás Real  3 , Juan Carlos Martín-Escudero  4 , Felipe Javier Chaves  6
Affiliations

Polymorphisms in endothelin system genes, arsenic levels and obesity risk

Vanesa Martínez-Barquero et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Linkage Disequilibrium (LD) plot of studied EDNRB SNPs. a) D´ b) R2.
See this image and copyright information in PMC

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