COC use and ESR1 genetic variants associated with the risk of stroke

Abstract

AbstractBackground Estrogen receptor α (ESR1) gene variation has been considered to be related to the development of cardiovascular disease. The aim of the present study is to determine the association ofESR1gene polymorphisms with risk of stroke and stroke subtypes in Chinese women, and further assess the gene-gene and gene-environment interactions betweenESR1gene and combined oral contraceptives (COC) on stroke risk. Methods A population-based case–control study was conducted. Three single nucleotide polymorphisms (SNPs) inESR1were genotyped in 453 first-ever stroke cases and 919 control subjects enrolled from our prospective female cohort, and information of contraceptive use was acquired by a face-to-face interview. Results AA genotype ofESR1rs4870056 compared with GG/GA genotypes was associated with a significantly decreased risk of hemorrhagic stroke (Recessive model:OR, 0.40; 95%CI, 0.20–0.82; qFDR = 0.036), while rs2228480 GA/AA genotype compared with GG genotype was found to be related to a slightly elevated risk of ischemic stroke (Dominant model:OR, 1.42; 95%CI, 1.02–1.97;P = 0.034). In addition, we identified significant gene-environment interactions between rs4870056 and COC use on stroke and ischemic stroke (Pinteraction=0.034 andPinteraction=0.012, respectively), but not on hemorrhagic stroke (Pinteraction=0.590). However, we found that rs4870056 GG/GA genotypes in combination with COC use jointly remarkably increased risk of hemorrhagic stroke (OR, 4.89; 95%CI, 1.82–13.13;P = 0.002). Conclusion Our findings suggested thatESR1rs4870056 polymorphism was significantly associated with hemorrhagic stroke in Chinese women, and the combined effect between GG/GA genotypes of rs4870056 and COC use could greatly increase the risk of hemorrhagic stroke.