title: Estrogen receptor α genetic variants and the risk of stroke in a South Indian population from Andhra Pradesh.
abstract: 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 α (ESR1) gene may influence stroke risk.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad-500016, India. anjanadurani@yahoo.co.in
authors.forename: Anjana
authors.initials: A
authors.lastname: Munshi
authors.forename: Vandana
authors.initials: V
authors.lastname: Sharma
authors.forename: Subhash
authors.initials: S
authors.lastname: Kaul
authors.forename: Amal
authors.initials: A
authors.lastname: Al-Hazzani
authors.forename: Ali A
authors.initials: AA
authors.lastname: Alshatwi
authors.forename: V Raj
authors.initials: VR
authors.lastname: Manohar
authors.forename: K
authors.initials: K
authors.lastname: Rajeshwar
authors.forename: M Sai
authors.initials: MS
authors.lastname: Babu
authors.forename: A
authors.initials: A
authors.lastname: Jyothy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015257:DNA-Cytosine Methylases / Q000235:genetics; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008593:Menopause; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D020521:Stroke / Q000145:classification / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D055815:Young Adult
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004958:Estradiol; C047084:DNA modification methylase PvuII; D015257:DNA-Cytosine Methylases