Estrogen receptor-alpha thymidine and adenine repeat polymorphism and endothelial fibrinolytic regulation in postmenopausal women.

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). 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. 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. 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.