Functional estrogen receptor alpha promoter polymorphism is associated with improved endothelial-dependent vasolidation

Figtree, G.A., Guzik, T., Robinson, B.G., Channon, K.M. and Watkins, H. (2010) Functional estrogen receptor alpha promoter polymorphism is associated with improved endothelial-dependent vasolidation. International Journal of Cardiology, 143(2), pp. 207-208. (doi: 10.1016/j.ijcard.2008.11.193) (PMID:19157583)

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Abstract

Estrogen receptor alpha (ERα) mediates beneficial actions on endothelial nitric oxide synthase (eNOS) and cholesterol metabolism. Genetic variations in the promoter of the ERα may therefore influence vascular function. We have identified a single nucleotide polymorphism (T > C) in the transcriptional element “ERNE” upstream of ERα which abolished the negative effect of this element in luciferase reporter assays and was associated with reduction in LDL cholesterol in a small association study. We have now examined for the association of this putative functional polymorphism with endothelial function. Endothelial-dependent relaxation (EDR) was measured in organ bath preparations of human saphenous vein obtained from 101 individuals (81 males and 20 females) undergoing coronary artery bypass surgery. The presence of the variant C allele was associated with enhanced EDR independently of hypercholesterolaemia, smoking and diabetes, as well as sex (ANOVA for ACh induced relaxation: p = 0.033). In males, the presence of the C allele was associated with a 225% augmentation of endothelial-dependent relaxation compared to wild-type (55.5 ± 10%; n = 3 vs. 24.7 ± 1%; n = 78; p < 0.001). In summary, a polymorphism in the ERα negative transcriptional element which results in increased transcription in vitro is associated with substantial augmentation of endothelial-dependent vasorelaxation.

Item Type:Articles (Letter)
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Guzik, Professor Tomasz
Authors: Figtree, G.A., Guzik, T., Robinson, B.G., Channon, K.M., and Watkins, H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:International Journal of Cardiology
Publisher:Elsevier Science B.V., Amsterdam.
ISSN:0167-5273
ISSN (Online):1874-1754
Published Online:20 January 2009

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