Raising interest towards genes implicates the effect of estrogen receptor-alpha (ESR1) gene on cerebrovascular disease, but data are lacking regarding the effect of estrogen receptor-beta (ESR2) gene. We assessed the hypothesis that AluI (G/A) polymorphism of the ESR2 gene (rs 4986938) is associated with ischemic stroke in a Caucasian population. Four hundred twenty four consecutive stroke patients and 430 age and gender-matched controls were enrolled in three stroke centers in Greece over one-year period. Patients and controls were compared in regard to the prevalence of the aforementioned polymorphism. No association was found between variations in the ESR2 gene and risk of stroke or stroke subtype in men and women. Of note, a gender-specific association of G allele with the onset of stroke at a younger age in male patients was found (63.68 ± 12.687 years in G allele (GG+AG) carriers vs. 68.95 ± 10.757 years in non-carriers (AA), p=0.008). Further population independent studies are needed to establish the role of ESR2 gene polymorphisms in relation to ischemic stroke in both genders. Such studies could lead to ERβ agonists being validated in individuals with certain genotypes and/or alleles towards the development of efficient strategies to preventing ischemic stroke in both men and women.
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