Oestrogen receptor polymorphisms are an associated risk factor for mild cognitive impairment and Alzheimer disease in women APOE {varepsilon}4 carriers: a case-control study.
OBJECTIVE
Examine the role of single nucleotide polymorphisms (SNPs) in the oestrogen receptor (ER) genes: rs9340799, rs2234693, rs2228480 (in the ESR1 gene) and rs4986938 (in the ESR2 gene) as a risk factor for amnesic mild cognitive impairment (MCIa) and Alzheimer's disease (AD) and its possible association with the apolipoprotein E (APOE) gene.


METHODS
We have investigated the independent and combined association of different alleles of the oestrogen receptor genes and APOE*ε4 allele with cognitive impairment using a case-control design.


METHODS
Participants were prospectively recruited from the neurology departments of several Basque Country hospitals.


METHODS
This study comprised 816 Caucasian participants who were aged 50 years and older: 204 MCIa, 350 sporadic patients with AD and 262 healthy controls.


METHODS
Clinical criteria and neuropsychological tests were used to establish the diagnostic groups (MCIa, AD and healthy controls). A dichotomous variable was used for each allele and genotype and the association with MCIa and AD was established using Logistic Regression Models.


RESULTS
Neither alleles nor genotypes of SNPs rs9340799, rs2234693, rs2228480 and rs4986938 of oestrogen receptor genes (ESR1 and ESR2) are independently associated with the risk of MCIa or AD. However, the genetic profile created with the combination of the less represented alleles of these SNPs (expressed as XPAA) was associated with an increased risk for MCIa (OR=3.30, 95% CI 1.28 to 8.54, p=0.014) and AD (OR=5.16, 95% CI 2.19 to 12.14, p<0.001) in women APOE*ε4 allele carriers.


CONCLUSIONS
The less represented alleles of SNPs studied are associated with MCIa and AD in APOE*E4 carriers. In particular, the genetic profile created with the less represented alleles of ESR1 and ESR2 SNPs are associated with an increased risk for MCIa and AD in women APOEε4 allele carriers.
Department of Neurology, Hospital Universitario Cruces, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain.
Manuel
M
Fernández-Martínez
Xabier
X
Elcoroaristizabal Martín
Elisa
E
Blanco Martín
Luis
L
Galdos Alcelay
Iratxe
I
Ugarriza Serrano
Fernando
F
Gómez Busto
Maite
M
Alvarez-Álvarez
Ana
A
Molano Salazar
Rocio
R
Bereincua Gandarias
Sandra
S
Inglés Borda
Juan María
JM
Uterga Valiente
Begoña
B
Indakoetxea Juanbeltz
María Ángeles
MÁ
Gómez Beldarraín
Josefa
J
Moraza López
Myriam
M
Barandiarán Amillano
Marian
M
M de Pancorbo
GENETICS