Estrogen receptor alpha gene variants are associated with Alzheimer's disease.
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.
Boada
Mercé
M
ACE Foundation, Catalan Institute of Applied Neurosciences, Barcelona, Spain.
Antunez
Carmen
C
López-Arrieta
Jesús
J
Caruz
Antonio
A
Moreno-Rey
Concha
C
Ramírez-Lorca
Reposo
R
Morón
Francisco Jesús
FJ
Hernández
Isabel
I
Mauleón
Ana
A
Rosende-Roca
Maiteé
M
Martínez-Lage
Pablo
P
Marín
Juan
J
Tárraga
Lluis
L
Alegret
Montserrat
M
Pedrajas
José Rafael
JR
Urda
Nuria
N
Royo
José Luis
JL
Saez
María Eugenia
ME
Gayán
Javier
J
González-Pérez
Antonio
A
Real
Luis Miguel
LM
Ruiz
Agustín
A
Galán
José Jorge
JJ
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
D053327:Apolipoprotein E4; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha