Estrogen receptor α genetic variants and the risk of stroke in a South Indian population from Andhra Pradesh

Background 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 alpha (ESR1) gene may influence stroke risk. Aims. The present study was carried out to investigate the role of ESR1 gene polymorphisms [Pvull (rs 2234693) and Xbal (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. Methods Four hundred patients with ischemic stroke and three hundred and eighty subjects were enrolled in this case-control study lschemic stroke subtypes were classified according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification The ESR1 Pvull and Xbal genotypes were determined by PCR-RFLP method Scrum estradiol was measured by ELISA Results. In case of Pvull 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 Xbal 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 Pvull 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 Pvull polymorphism with extracranial atherosclerosis, lacunar and cardioembolic stroke Conclusion. In conclusion our results suggest the Pvull gene polymorphism is significantly associated with stroke in postmenopausal women in a South Indian population from Andhra Pradesh The pp genotypes have average 17 beta 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. (C) 2010 Elsevier B.V. All rights reserved.