Format

Send to

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

Polymorphisms in endothelin system genes, arsenic levels and obesity risk.

Author information

1
Department of Medicine, University of Valencia, Valencia, Spain; Genotyping and Genetic Diagnosis Unit, Hospital Clínico Research Foundation (INCLIVA), Valencia, Spain.
2
Genotyping and Genetic Diagnosis Unit, Hospital Clínico Research Foundation (INCLIVA), Valencia, Spain.
3
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.
4
Internal Medicine, Rio Hortega Hospital, University of Valladolid, Valladolid, Spain.
5
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.
6
Genotyping and Genetic Diagnosis Unit, Hospital Clínico Research Foundation (INCLIVA), Valencia, Spain; CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain.

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.

PMID:
25799405
PMCID:
PMC4370725
DOI:
10.1371/journal.pone.0118471
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center