Polymorphisms in Endothelin System Genes, Arsenic Levels and Obesity Risk

Abstract

Background/ObjectivesObesity 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/MethodsWe 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.ResultsWe 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)ConclusionsOur results support the hypothesis that polymorphisms of the EDNRB gene may influence the susceptibility to obesity and can interact with plasma arsenic levels.

Elevated plasma endothelin-1 is associated with reduced weight loss post vertical sleeve gastrectomy

“…On the other hand, activation of the ET B receptor blocks the antilipolytic effect of insulin [9]. Moreover, a single nucleotide polymorphism in the ET B receptor is associated with reduced risk of obesity in 2 separate populations in Spain [28]. Taken together, these data suggest that higher plasma ET-1 may inhibit weight loss after bariatric surgery.…”

Pathogenetic Role of Endotelin-1 and Polymorphism of Its Receptors in Diabetes Mellitus Type 2

“…Численні дані щодо ролі поліморфізмів генів ендотелінових рецепторів у цілій низці судинних захворювань та їх залежність від етнічної приналежності хворих [11][12][13][14], дало поштовх до вивчення цього питання у хворих на ЦД2Т з української популяції. Слід відмітити, що за таблицею спряженості (3×3) був показаний зв'язок генотипів rs6842241 гена EDNRA з захворюванням (χ 2 =6,67; P=0,035).…”

“…Іспанські дослідники [11] встановили, що деякі поліморфізми в системі генів ендотелінових рецепторів можуть бути пов'язані з ожирінням. Це було підтверджено відносно поліморфізму rs5351 гена EDNRB, який сприяв зниженню ризику ожиріння.…”

Determination of Arsenic and Health Risk Assessment in the Ground Water of Sindh, Pakistan

“…Illness characteristic of long-term arsenic exposure comes in the form of skin cancer, bladder cancer, inactivation of an enzyme system in the body, black foot disease, and obesity [1][2][3]. As contact can also cause other health consequences such as gastrointestinal irritation, diabetes, less number of white and red blood cells, hypertension, blood vessels rupture and abnormal heart beats [4].…”