TY - JOUR
T1 - Estrogen receptor polymorphisms and incident dementia
T2 - The prospective 3C study
AU - Ryan, Joanne
AU - Carrière, Isabelle
AU - Carcaillon, Laure
AU - Dartigues, Jean-Francois
AU - Auriacombe, Sophie
AU - Rouaud, Olivier
AU - Berr, Claudine
AU - Ritchie, Karen
AU - Scarabin, Pierre Yves
AU - Ancelin, Marie Laure
PY - 2014/1
Y1 - 2014/1
N2 - Background: Genetic variation in the estrogen receptor (ESR) may be associated with the incidence of Alzheimer's disease (AD), but this association could be modified by genetic and environmental factors. Methods: The association between five ESR α (ESR1) and β (ESR2) polymorphisms with 7-year dementia incidence was examined among 6959 older men and women from the Three City Study using multivariate-adjusted Cox regression models with delayed entry. Gender, the apolipoprotein E (APOE) ε4 allele, and hormone treatment were considered as potential effect modifiers of this association. Results: Among women, the CC genotype of ESR1 rs2234693 was specifically associated with a small increased risk of AD (adjusted hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.03-2.28, P =.03). However, women with this genotype had a substantially increased risk of AD associated with the APOE ε4 allele (adjusted HR: 3.24, 95% CI: 1.81-5.79 for women rs2234693 CC; compared with HR: 1.87, 95% CI: 1.37-2.56 for all women). There was also evidence of a nominally significant interaction between the ESR1 and ESR2 polymorphisms on the risk of all dementias (P =.04). Hormone treatment did not modify these associations, and there were no significant associations in men. Conclusions: Although there was only weak support for a gender-specific association between the common ESR1 rs2234693 polymorphism and AD, this polymorphism may act as an effect modifier, modifying the association between an ESR2 polymorphism and dementia, as well as the risk of AD associated with the APOE ε4 allele.
AB - Background: Genetic variation in the estrogen receptor (ESR) may be associated with the incidence of Alzheimer's disease (AD), but this association could be modified by genetic and environmental factors. Methods: The association between five ESR α (ESR1) and β (ESR2) polymorphisms with 7-year dementia incidence was examined among 6959 older men and women from the Three City Study using multivariate-adjusted Cox regression models with delayed entry. Gender, the apolipoprotein E (APOE) ε4 allele, and hormone treatment were considered as potential effect modifiers of this association. Results: Among women, the CC genotype of ESR1 rs2234693 was specifically associated with a small increased risk of AD (adjusted hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.03-2.28, P =.03). However, women with this genotype had a substantially increased risk of AD associated with the APOE ε4 allele (adjusted HR: 3.24, 95% CI: 1.81-5.79 for women rs2234693 CC; compared with HR: 1.87, 95% CI: 1.37-2.56 for all women). There was also evidence of a nominally significant interaction between the ESR1 and ESR2 polymorphisms on the risk of all dementias (P =.04). Hormone treatment did not modify these associations, and there were no significant associations in men. Conclusions: Although there was only weak support for a gender-specific association between the common ESR1 rs2234693 polymorphism and AD, this polymorphism may act as an effect modifier, modifying the association between an ESR2 polymorphism and dementia, as well as the risk of AD associated with the APOE ε4 allele.
KW - Alzheimer's disease
KW - APOE
KW - Cohort study
KW - Dementia
KW - Epidemiology
KW - ESR1
KW - ESR2
KW - Estrogen receptor polymorphisms
KW - Gender-specific
UR - http://www.scopus.com/inward/record.url?scp=84891149125&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2012.12.008
DO - 10.1016/j.jalz.2012.12.008
M3 - Article
C2 - 23491264
AN - SCOPUS:84891149125
VL - 10
SP - 27
EP - 35
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
IS - 1
ER -