Introduction: The vascular protective effects of estrogens are known to be mediated by their binding to specific estrogen receptors (ER). However, the significance of genetic variations of the ER in vascular diseases has not been reported. We have examined the association between stroke and PvuII and XbaI polymorphisms of the estrogen receptor-alpha gene in patients with metabolic syndrome.
Methods and subjects: The study population consisted by 84 male and 46 female patients with metabolic syndrome compared with 100 healthy men and 140 healthy women respectively. The body mass index was recorded and biochemical parameters were measured. PCR-RFLP and genotyping of ER PvuII and XbaI polymorphisms were performed in peripheral blood leucocytes. Multiple logistic regression analysis was used to explore the risk factors for stroke. Local Ethical Committee approval was obtained.
Results: Both polymorphisms were in Hardy Weinberg equilibrium in the study population. Genotype distributions and allele frequencies of PvuII or XbaI polymorphisms were not significantly different between control subjects and patients. No association was found between the polymorphisms and the severity of stroke. Total cholesterol, triglyceride, or HDL-cholesterol levels were not significantly different among ER genotypes. However, men homozygous for A allele of XbaI polymorphism had a stroke at a younger age compared to other genotypes (53,3±8,1 years vs 56,9±9,4 years, P<0,05).
Conclusion: These findings suggest that PvuII and XbaI polymorphisms of ER are not associated with the prevalence and severity of cerebrovascular disease. However, the XbaI polymorphism seems to affect the age of developing cerebrovascular disease in men with metabolic syndrome.