title: Estrogen receptor alpha gene variants are associated with Alzheimer's disease.
abstract: The present research is aimed at assessing the role of 3 estrogen receptor alpha (ESR1) gene variants in late onset Alzheimer's disease (AD) susceptibility. One thousand one hundred thirteen unrelated late onset sporadic AD patients, 1109 healthy controls and 121 neurologically healthy elderly controls were used to carry out case-control genetic association studies with ESR1 rs3844508, rs2234693, and ESR1 noncoding deletion 1 (ESR1-NCD1) polymorphisms. Thirty-five healthy male samples were used for molecular analyses. The rs2234693 polymorphism is associated with AD in our population (odds ratio [OR], 1.29; p = 0.008). The rs3844508 marker confers protection against AD in males (OR, 0.57; p = 0.001) and the deletion ESR1-NCD1 is a risk factor for AD in women (OR, 1.67; p < 0.001). Molecular analyses on ESR1-NCD1 indicate that this deletion confers a higher response to estradiol activity on ESR1 receptor and it is also associated with differential expression of ESR1 isoforms. Our results support the involvement of ESR1 gene in AD and point to the existence of sexual dimorphism for ESR1 markers. In addition, carriers of ESR1-NCD1 deletion could overrespond to estradiol action.
authors.affiliation: ACE Foundation, Catalan Institute of Applied Neurosciences, Barcelona, Spain.
authors.forename: Mercé
authors.initials: M
authors.lastname: Boada
authors.forename: Carmen
authors.initials: C
authors.lastname: Antunez
authors.forename: Jesús
authors.initials: J
authors.lastname: López-Arrieta
authors.forename: Antonio
authors.initials: A
authors.lastname: Caruz
authors.forename: Concha
authors.initials: C
authors.lastname: Moreno-Rey
authors.forename: Reposo
authors.initials: R
authors.lastname: Ramírez-Lorca
authors.forename: Francisco Jesús
authors.initials: FJ
authors.lastname: Morón
authors.forename: Isabel
authors.initials: I
authors.lastname: Hernández
authors.forename: Ana
authors.initials: A
authors.lastname: Mauleón
authors.forename: Maiteé
authors.initials: M
authors.lastname: Rosende-Roca
authors.forename: Pablo
authors.initials: P
authors.lastname: Martínez-Lage
authors.forename: Juan
authors.initials: J
authors.lastname: Marín
authors.forename: Lluis
authors.initials: L
authors.lastname: Tárraga
authors.forename: Montserrat
authors.initials: M
authors.lastname: Alegret
authors.forename: José Rafael
authors.initials: JR
authors.lastname: Pedrajas
authors.forename: Nuria
authors.initials: N
authors.lastname: Urda
authors.forename: José Luis
authors.initials: JL
authors.lastname: Royo
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Saez
authors.forename: Javier
authors.initials: J
authors.lastname: Gayán
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Pérez
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Real
authors.forename: Agustín
authors.initials: A
authors.lastname: Ruiz
authors.forename: José Jorge
authors.initials: JJ
authors.lastname: Galán
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012727:Sex Characteristics
chemical_list: D053327:Apolipoprotein E4; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha