Estrogen receptor-α 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 (≥18 repeats). Study design 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, ≥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. Conclusion 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.