Functional estrogen receptor alpha promoter polymorphism is associated with improved endothelial-dependent vasolidation.
Estrogen receptor alpha (ERalpha) mediates beneficial actions on endothelial nitric oxide synthase (eNOS) and cholesterol metabolism. Genetic variations in the promoter of the ERalpha may therefore influence vascular function. We have identified a single nucleotide polymorphism (T>C) in the t...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2010
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| _version_ | 1797071153051729920 |
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| author | Figtree, G Guzik, T Robinson, BG Channon, K Watkins, H |
| author_facet | Figtree, G Guzik, T Robinson, BG Channon, K Watkins, H |
| author_sort | Figtree, G |
| collection | OXFORD |
| description | Estrogen receptor alpha (ERalpha) mediates beneficial actions on endothelial nitric oxide synthase (eNOS) and cholesterol metabolism. Genetic variations in the promoter of the ERalpha may therefore influence vascular function. We have identified a single nucleotide polymorphism (T>C) in the transcriptional element "ERNE" upstream of ERalpha 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 ERalpha negative transcriptional element which results in increased transcription in vitro is associated with substantial augmentation of endothelial-dependent vasorelaxation. |
| first_indexed | 2024-03-06T22:49:10Z |
| format | Journal article |
| id | oxford-uuid:5e3b1295-7eb7-4234-9820-fb894369dd21 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:49:10Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:5e3b1295-7eb7-4234-9820-fb894369dd212022-03-26T17:39:13ZFunctional estrogen receptor alpha promoter polymorphism is associated with improved endothelial-dependent vasolidation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5e3b1295-7eb7-4234-9820-fb894369dd21EnglishSymplectic Elements at Oxford2010Figtree, GGuzik, TRobinson, BGChannon, KWatkins, HEstrogen receptor alpha (ERalpha) mediates beneficial actions on endothelial nitric oxide synthase (eNOS) and cholesterol metabolism. Genetic variations in the promoter of the ERalpha may therefore influence vascular function. We have identified a single nucleotide polymorphism (T>C) in the transcriptional element "ERNE" upstream of ERalpha 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 ERalpha negative transcriptional element which results in increased transcription in vitro is associated with substantial augmentation of endothelial-dependent vasorelaxation. |
| spellingShingle | Figtree, G Guzik, T Robinson, BG Channon, K Watkins, H Functional estrogen receptor alpha promoter polymorphism is associated with improved endothelial-dependent vasolidation. |
| title | Functional estrogen receptor alpha promoter polymorphism is associated with improved endothelial-dependent vasolidation. |
| title_full | Functional estrogen receptor alpha promoter polymorphism is associated with improved endothelial-dependent vasolidation. |
| title_fullStr | Functional estrogen receptor alpha promoter polymorphism is associated with improved endothelial-dependent vasolidation. |
| title_full_unstemmed | Functional estrogen receptor alpha promoter polymorphism is associated with improved endothelial-dependent vasolidation. |
| title_short | Functional estrogen receptor alpha promoter polymorphism is associated with improved endothelial-dependent vasolidation. |
| title_sort | functional estrogen receptor alpha promoter polymorphism is associated with improved endothelial dependent vasolidation |
| work_keys_str_mv | AT figtreeg functionalestrogenreceptoralphapromoterpolymorphismisassociatedwithimprovedendothelialdependentvasolidation AT guzikt functionalestrogenreceptoralphapromoterpolymorphismisassociatedwithimprovedendothelialdependentvasolidation AT robinsonbg functionalestrogenreceptoralphapromoterpolymorphismisassociatedwithimprovedendothelialdependentvasolidation AT channonk functionalestrogenreceptoralphapromoterpolymorphismisassociatedwithimprovedendothelialdependentvasolidation AT watkinsh functionalestrogenreceptoralphapromoterpolymorphismisassociatedwithimprovedendothelialdependentvasolidation |