Background and aim: There is accumulating evidence suggesting an important role of estrogen receptor-β in the development of cardiovascular disease. The present study aims to investigate the relationship of estrogen receptor β gene (ESR2) polymorphisms with stroke risk in Chinese women, and further evaluate the gene-environment interaction of ESR2 and combined oral contraceptive (COC) use on stroke risk.
Methods: A case-control study was conducted with 446 first-ever stroke patients and 864 control subjects recruited from our prospective female cohort. Four polymorphisms of ESR2 gene were genotyped, and the information of contraceptive use was obtained by a face-to-face interview.
Results: Women with rs1256065 CC genotype were at a 1.59 fold increased risk of stroke. Subtype analyses showed that the risk genotype of rs1256065 was associated with ischemic stroke, but not with hemorrhagic stroke. AA genotype of rs4986938 showed a significant correlation with an elevated risk of hemorrhagic stroke. COC users with rs1256065 CC genotype had a 2.36 fold increased risk of stroke, compared with the non-users with the wild-type genotype. Moreover, a significant multiplicative interaction on hemorrhagic stroke was detected between COC use and rs4986938 (pinteraction = 0.023). The risk of hemorrhagic stroke was significantly elevated among carriers of rs4986938 GA or AA genotype combined with COC use. No associations were observed for rs1256049 and rs1271572.
Conclusions: ESR2 genetic polymorphisms were associated with the risk of first-ever stroke in Chinese women, and the AA genotype of rs4986938 combined with COC use could significantly increase the risk of hemorrhagic stroke.
Keywords: Estrogen receptor β gene; Oral contraceptives; Single nucleotide polymorphism; Stroke.
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