title: Estrogen receptor beta gene variant is associated with vascular dementia in elderly women.
abstract: OBJECTIVE
  Alzheimer's disease (AD) and vascular dementia (VaD) are the main causes of dementia. Postmenopausal estrogen deficiency was suggested as a contributor to cognitive decline; however, replacement therapy failed to prove beneficial in its prevention or therapy. Sequence variants in the estrogen receptor alpha gene (ESR1) and beta gene (ESR2) may alter the effects of estrogen.
  
  
  METHODS
  This is a case-control association study of sporadic AD, VaD, and single-nucleotide polymorphisms in ESR1 (rs2234693 and rs9340799), the TA dinucleotide repeat in the ESR1 promoter, and the rs4986938 single-nucleotide polymorphism in ESR2. Two hundred forty-six women (118 AD, age 83 +/- 7; 60 VaD, age 82 +/- 6; and 68 cognitively intact, age 81 +/- 7) residing in nursing homes were studied. The association of genotypes and AD or VaD was determined by logistic regression analysis adjusted for age and ethnic origin.
  
  
  RESULTS
  An association of VaD and ESR2 rs4986938 was found. Carriers of each A allele had a 1.7 increased risk compared to carriers of the G allele (odds ratio 1.71, 95% confidence interval 1-2.95). The ApoE epsilon 4 allele was associated with AD (odds ratio 3.35, confidence interval 1.44-7.82), but not with VaD. No association of AD or VaD with ESR1 genotypes or haplotypes was detected.
  
  
  CONCLUSIONS
  The ESR2 rs4986938 polymorphism is associated with susceptibility for VaD in elderly Jewish women. These results need to be confirmed in replicate studies in other populations.
authors.affiliation: Endocrinology and Metabolism Service, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. rivkap@hadassah.org.il
authors.forename: Rivka
authors.initials: R
authors.lastname: Dresner-Pollak
authors.forename: Talia
authors.initials: T
authors.lastname: Kinnar
authors.forename: Yechiel
authors.initials: Y
authors.lastname: Friedlander
authors.forename: Nir
authors.initials: N
authors.lastname: Sharon
authors.forename: Hanna
authors.initials: H
authors.lastname: Rosenmann
authors.forename: Arthur
authors.initials: A
authors.lastname: Pollak
mesh_terms: D000369:Aged, 80 and over; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D015140:Dementia, Vascular / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D007557:Israel; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D001057:Apolipoproteins E; D047629:Estrogen Receptor beta