Estrogen receptor α genetic variants and the risk of stroke in a South Indian population from Andhra Pradesh.
ABSTRACT Stroke is a complex disease caused by combination of multiple risk factors. Recent findings have suggested that stroke has a strong genetic component. Evidence suggests that variations in the estrogen receptor α (ESR1) gene may influence stroke risk.
The present study was carried out to investigate the role of ESR1 gene polymorphisms [PvuII (rs 2234693) and XbaI (rs 9340799)] with stroke in a South Indian population from Andhra Pradesh. The relationship between ESR1 genotypes with estradiol levels was also investigated in pre- and postmenopausal women.
Four hundred patients with ischemic stroke and three hundred and eighty subjects were enrolled in this case-control study. Ischemic stroke subtypes were classified according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. The ESR1 PvuII and XbaI genotypes were determined by PCR-RFLP method. Serum estradiol was measured by ELISA.
In case of PvuII polymorphism statistically significant difference was observed in the genotypic and allelic frequencies between patients and controls (joint analysis of men and women) (p=0.003 and 0.004 respectively). However, the XbaI genotypes and alleles did not show an association with stroke in the study population. When the analysis was carried out separately for men and women, the PvuII polymorphism did not show significant association with stroke in men; women showed a significant association. Further when women were grouped in to premenopausal and postmenopausal, the premenopausal group did not show a significant association with the polymorphism but significant association with stroke was found in postmenopausal women. A stepwise multiple logistic regression analysis confirmed these findings. Women with pp genotype had low estradiol levels in comparison with PP genotypic individuals (p<0.05). Further evaluating the association of this polymorphism with stroke subtypes, we found significant association of PvuII polymorphism with extracranial atherosclerosis, lacunar and cardioembolic stroke.
In conclusion our results suggest the PvuII gene polymorphism is significantly associated with stroke in postmenopausal women in a South Indian population from Andhra Pradesh. The pp genotypes have average 17β estradiol levels which are significantly low in comparison with PP genotypes. Therefore postmenopausal women with a high frequency of pp genotype are more predisposed to ischemic stroke. However, this is a preliminary study and the results need to be confirmed in a larger cohort.
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ABSTRACT: A number of studies have documented that estrogen receptor α (ESR1) may play an important role in the development and progression of cerebral infarction, but many existing studies have yielded inconclusive results. This meta-analysis was performed to evaluate the relationships between ESR1 genetic polymorphisms and cerebral infarction risk. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before October 1, 2013, without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Seven case-control studies were included with a total of 1471 patients with cerebral infarction and 4688 healthy control subjects. Two common single-nucleotide polymorphisms (SNPs) in the ESR1 gene (rs2234693 T>C and rs9340799 A>G) were assessed. Our meta-analysis results revealed that ESR1 genetic polymorphisms might increase the risk of cerebral infarction. Subgroup analysis by SNP type indicated that both rs2234693 and rs9340799 polymorphisms in the ESR1 gene were strongly associated with an increased risk of cerebral infarction. Further subgroup analysis by ethnicity showed significant associations between ESR1 genetic polymorphisms and increased risk of cerebral infarction among both Asians and Caucasians. In the stratified subgroup analysis by gender, the results suggested that ESR1 genetic polymorphisms were associated with an increased risk of cerebral infarction in the female population. However, there were no statistically significant associations between ESR1 genetic polymorphisms and cerebral infarction risk in the male population. Meta-regression analyses also confirmed that gender might be a main source of heterogeneity. Our findings indicate that ESR1 genetic polymorphisms may contribute to the development of cerebral infarction, especially in the female population.DNA and cell biology 04/2014; · 2.28 Impact Factor
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ABSTRACT: Abstract Several studies have examined the association of the PvuII polymorphism of the estrogen receptor alpha gene with the risk of stroke. Data linking the polymorphism with the severity and outcome of cerebrovascular disease are lacking. In this study, we evaluated 285 postmenopausal Caucasian patients suffering an acute stroke, hospitalized in two tertiary hospitals over a period of 2 years, and searched for associations between the PvuII polymorphism and the one-month outcome and the neurological severity on admission. The prevalence of CC genotype was 21%, CT 50% and TT 29%. Estradiol levels were higher with increasing frequencies of the C allele (p = 0.04). There was no difference in the short-term functional outcome and mortality and the neurological severity on admission among the three genotypes. We did not find a significant association of the PvuII polymorphism with intracerebral hemorrhage and classical stroke risk factors. An association of the CC genotype with venous thromboembolism history was recorded (p 0.05). There was no association between the PvuII polymorphism and stroke severity and short-term outcome in the studied female stroke population. It is possible that the long-term estrogenic action, reflected by the genetic polymorphism, is not a major determinant of disease severity and prognosis in older age.Gynecological Endocrinology 06/2013; · 1.30 Impact Factor
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ABSTRACT: E-selectin is an important inflammatory cytokine involved in the pathogenesis of various diseases such as atherosclerosis and stroke. We investigated the association of E-selectin gene polymorphism (S128R) with ischemic stroke and its subtypes. We studied 610 patients with ischemic stroke and 610 age- and sex-matched healthy controls. The ischemic stroke was classified according to Trial of Org10172 in Acute Stroke Treatment (TOAST). E-selectin gene polymorphism (S128R) was determined by polymerase chain reaction-restriction fragment length polymorphism technique. We found statistically significant difference in the genotypic distribution between patients and controls (for AC vs. AA, χ (2) = 49.5; p < 0.001, odds ratio = 5.47(95 % CI, 3.25-9.21). A significant difference was observed in the frequency of C and A alleles in patients and controls (for C vs. A, χ (2) = 47.4; p < 0.001, odds ratio = 5.13 (95 % CI, 3.06-8.57). Multiple logistic regression analysis revealed that the most predictive risk factor for stroke was AC genotype (adjusted odds ratio = 1.450 (95 % CI, 1.23-2.75) and p = 0.001), hypertension, smoking, and diabetes (p = 0.001 in each case). We also found a significant association of AC genotype with intracranial large artery atherosclerosis (p < 0.01, odds ratio = 9.37, (95 % CI, 5.31-16.5) and small artery occlusion (p < 0.0001, odds ratio = 9.81 (95 % CI, 4.94-19.4). Our results indicate that the individuals bearing AC genotype of E-selectin gene polymorphism (S128R) are more prone to stroke than AA genotype.Inflammation 11/2013; · 2.46 Impact Factor