Abstract
BackgroundEndogenous estrogens play an important role in the overall cardiocirculatory system. However, there are no studies exploring the hormone metabolism and signaling pathway genes together on ischemic stroke, including sulfotransferase family 1E (SULT1E1), catechol-O-methyl-transferase (COMT), and estrogen receptor α (ESR1).MethodsA case-control study was conducted on 305 young ischemic stroke subjects aged ≦ 50 years and 309 age-matched healthy controls. SULT1E1 -64G/A, COMT Val158Met, ESR1 c.454−397 T/C and c.454−351 A/G genes were genotyped and compared between cases and controls to identify single nucleotide polymorphisms associated with ischemic stroke susceptibility. Gene-gene interaction effects were analyzed using entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional multiple regression models.ResultsCOMT Val158Met polymorphism showed a significant association with susceptibility of young ischemic stroke among females. There was a two-way interaction between SULT1E1 -64G/A and COMT Val158Met in both MDR and CART analysis. The logistic regression model also showed there was a significant interaction effect between SULT1E1 -64G/A and COMT Val158Met on ischemic stroke of the young (P for interaction = 0.0171). We further found that lower estradiol level could increase the risk of young ischemic stroke for those who carry either SULT1E1 or COMT risk genotypes, showing a significant interaction effect (P for interaction = 0.0174).ConclusionsOur findings support that a significant epistasis effect exists among estrogen metabolic and signaling pathway genes and gene-environment interactions on young ischemic stroke subjects.
Highlights
Previous population-based epidemiological studies reported stroke incidence rate to be lower in women during midlife than that in either older aged women or men [1,2]
Mean Body mass index (BMI), Waist-to-hip ratio (WHR), fasting glucose levels, Low-density lipoprotein cholesterol (LDLC), and TG were significantly higher in cases than in controls while HDLC were lower in cases compared to controls
To determine the ischemic stroke risk contribution of SULT1E1, COMT and ESR1, we examined whether the genotypic and allelic distribution of the gene differed between the 305 cases and 309 controls (301 cases and 308 controls had results of complete 4 single nucleotide polymorphism (SNP))
Summary
Previous population-based epidemiological studies reported stroke incidence rate to be lower in women during midlife than that in either older aged women or men [1,2]. In addition to experimental studies demonstrating the protective roles of estrogens in many forms of cardiovascular and cerebrovascular diseases [3,4,5], a large volume of epidemiological and observational findings indicate that exposure to endogenous estrogen has been postulated to be protective for stroke in premenopausal women [6,7]. Since abundant evidence demonstrates that estrogen might play an important role in the overall cardiocirculatory system, understanding the estrogen metabolic and signaling pathway in relation to vascular disease may shed light on the role of estrogen in ischemic stroke pathogenesis. We focused on 3 genes involved in steroid hormone metabolism and signaling: sulfotransferase family 1E (SULT1E1), catechol-Omethyl-transferase (COMT), and estrogen receptor a (ESR1). There are no studies exploring the hormone metabolism and signaling pathway genes together on ischemic stroke, including sulfotransferase family 1E (SULT1E1), catechol-O-methyl-transferase (COMT), and estrogen receptor a (ESR1)
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