Progression from amnesic mild cognitive impairment to Alzheimer's disease: ESR1 and ESR2 polymorphisms and APOE gene.
BACKGROUND
Many genes have been studied to determine how they might be involved in Alzheimer's disease (AD). Estrogens have a protective effect in the central nervous system. The mechanisms of action of estrogens are mediated by two estrogen receptors (ERs), ERα and ERβ. Thus, these genes could also play a role in the progression of amnesic mild cognitive impairment (MCIa) to AD. The aim of this study was to examine the role of ER single nucleotide polymorphisms (SNPs) as a risk factor for MCIa, as well as the interaction with apolipoprotein E (APOE) ε4 in the progression to AD.


METHODS
79 MCIa patients and 138 healthy controls were analyzed. SNPs were genotyped via restriction fragment length polymorphisms and real-time PCR, RT-PCR or RT-PCR (TaqMan) assays.


RESULTS
There is a lack of association between MCIa patients who converted to AD and ER SNPs. APOE ε4 allele is an independent risk factor of MCIa (OR=1.86; 95% CI=1.02-3.38, p=0.042) with a high prevalence in converted subjects. APOE ε4 is able to predict the progression from MCIa patients to AD (OR=2.55; 95% CI=1.20-5.42, p=0.015).


CONCLUSIONS
The presence of the APOE ε4 allele, and not the alleles of ER SNPs, is a risk factor for MCIa. Furthermore, APOE genotype seems to predict the conversion from MCIa to AD.
BIOMICS Research Group, Department of Zoology and Cellular Biology A, Centro de Investigación y Estudios Avanzados Lucio Lascaray (CIEA), University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain.
X
X
Elcoroaristizabal Martín
M
M
Fernández Martínez
L
L
Galdos Alcelay
A
A
Molano Salazar
R
R
Bereincua Gandarias
S
S
Inglés Borda
F
F
Gómez Busto
J M
JM
Uterga Valiente
B
B
Indakoetxea Juanbeltz
M A
MA
Gómez Beldarraín
M M
MM
de Pancorbo
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000235:genetics*; D018450:Disease Progression; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016016:Proportional Hazards Models; D012307:Risk Factors
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta