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  • Title: ESR2 Genetic Variants and Combined Oral Contraceptive Use Associated with the Risk of Stroke.
    Author: Xu Z, Li Y, Huang X, Shen W, Bai J, Shen C, Zhao Y.
    Journal: Arch Med Res; 2017 Feb; 48(2):203-211. PubMed ID: 28625324.
    Abstract:
    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.
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