Dataset Information

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

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.

SUBMITTER: Martinez-Barquero V

PROVIDER: S-EPMC4370725 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

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

Martínez-Barquero Vanesa V de Marco Griselda G Martínez-Hervas Sergio S Rentero Pilar P Galan-Chilet Inmaculada I Blesa Sebastian S Morchon David D Morcillo Sonsoles S Rojo Gemma G Ascaso Juan Francisco JF Real José Tomás JT Martín-Escudero Juan Carlos JC Chaves Felipe Javier FJ

PloS one 20150323 3

<h4>Background/objectives</h4>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, th ...[more]

PMID: 25799405

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Project description:The purpose of this study was to determine whether four single nucleotide polymorphisms (SNPs) of endothelin and endothelin receptor type A genes can constitute a risk factor for normal tension glaucoma (NTG) and high tension glaucoma (HTG).The study included 160 patients with NTG, 124 patients with HTG, and 165 healthy controls. To analyze the frequency of polymorphic variants of the endothelin EDN gene (K198N) and the endothelin receptor type A gene EDN RA (C1222T, C70G, G231A), DNA was isolated from peripheral blood, and SNP genotyping was performed using the real-time PCR (RT-PCR) method. Plasma endothelin (ET) concentrations were detected using an enzyme immunoassay. Endothelin levels were compared with genotype and allele distributions, patients' clinical status, and various risk factors for NTG.There was a significant difference between the patients with NTG and HTG and the controls (p = 0.035, p = 0.008) regarding the genotype of the C1222T and C70G polymorphism. Plasma concentrations of ET did not differ between the NTG and HTG groups, and no significant correlation with intraocular pressure (IOP), best-corrected visual acuity (BCVA), and the cup to disc ratio (c/d ratio) was seen in patients with NTG. Plasma endothelin levels showed a noticeably positive correlation with age in the NTG group (R = 0.249, p = 0.042). Higher endothelin levels corresponded to more advanced visual field damage. No statistical difference was observed between variant genotypes of K198N and the ET-1 plasma concentration in patients with NTG, whereas a slightly higher ET level was observed in the patients with HTG with the GT genotype in comparison to those with the GG genotype (p = 0.001). The C1222T polymorphism significantly affected the plasma ET level in patients with NTG. The TT genotype carriers had the highest ET level, and the CC genotype carriers the lowest (p = 0.034). The AA variant genotype of the G231A polymorphism exhibited the highest ET level, while the GG variant genotype represented the lowest level (p = 0.033). No significant differences were observed regarding the endothelin levels and the frequency of notches, peripapillary atrophy, low blood pressure, cold extremities, or migraine in the two groups studied. Slightly lower endothelin plasma levels were observed in patients with optic disc hemorrhages in the NTG group (p = 0.05).Polymorphic variants of endothelin EDN (K198N) and endothelin receptor type A genes EDN RA (C1222T, C70G, G231A) affected ET plasma concentrations. There was no association between the plasma endothelin levels and the risk factors for NTG. According to these results, plasma endothelin concentrations do not appear to be a marker for NTG.

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Dataset Information

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

Background/objectives

Subjects/methods

Results

Conclusions

Publications

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

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