Estrogen receptor-alpha thymidine and adenine repeat polymorphism and endothelial fibrinolytic regulation in postmenopausal women.
OBJECTIVE
We hypothesized that the capacity of the endothelium to release tissue-type plasminogen activator is blunted in postmenopausal women with long (TA)(n) repeat alleles (> or = 18 repeats).


METHODS
Forty-two healthy postmenopausal women were studied: 10 women with short allele genotypes (both alleles, <18 repeats; age, 59 +/- 2 years), 8 women with long allele genotypes (both alleles, > or = 18 repeats; age, 59 +/- 3 years), and 24 women with mixed allele genotypes (1 short and 1 long allele; age, 56 +/- 1 years). Net endothelial tissue-type plasminogen activator release was determined in response to intra-arterial bradykinin and sodium nitroprusside.


RESULTS
Tissue-type plasminogen activator release in response to bradykinin was highest in homozygotes for the short allele. The total amount of tissue-type plasminogen activator antigen that was released was significantly higher (>55%) in the short (452 +/- 68 ng/100 mL tissue) compared with the mixed (248 +/- 27 ng/100 mL tissue) and long allele (290 +/- 53 ng/100 mL tissue) groups.


CONCLUSIONS
Our results demonstrate that the long (TA)n dinucleotide repeat allele is associated with blunted endothelial tissue-type plasminogen activator release in healthy postmenopausal women.
Hoetzer
Greta L
GL
Department of Integrative Physiology, Integrative Vascular Biology Laboratory, University of Colorado, Boulder, CO 80309, USA. greta.hoetzer@colorado.edu
Irmiger
Heather M
HM
Stauffer
Brian L
BL
DeSouza
Christopher A
CA
D000225:Adenine / Q000502:physiology; D018900:Dinucleotide Repeats / Q000502:physiology*; D004727:Endothelium / Q000378:metabolism / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause / Q000235:genetics / Q000502:physiology*; D013936:Thymidine / Q000235:genetics; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D010959:Tissue Plasminogen Activator; D000225:Adenine; D013936:Thymidine