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01-12-2016 | Translational Neurosciences - Original Article

Estrogen receptor beta polymorphisms and cognitive performance in women: associations and modifications by genetic and environmental influences

Authors: Karin Fehsel, Tamara Schikowski, Michaela Jänner, Anke Hüls, Mohammed Voussoughi, Thomas Schulte, Andrea Vierkötter, Tom Teichert, Christian Herder, Dorothea Sugiri, Ursula Krämer, Christian Luckhaus

Published in: Journal of Neural Transmission | Issue 12/2016

Abstract

Genetic and environmental risk factors contribute to the pathogenesis of Alzheimer’s dementia. Besides known genetic risk factors like the apolipoprotein (APO) Eε4 allele, single nuclear polymorphisms (SNPs) of the estrogen receptors (ESRs) are candidate genetic risk factors, while air pollution represents an environmental risk factor for dementia. Effects of these risk factors and their interaction were investigated in the SALIA cohort of 834 non-demented elderly women. Cognitive function was assessed by the CERAD-plus test battery. Air pollution was estimated by land use regression (LUR) models. Genotyping was carried out for nine ESR1 and ESR2 SNPs and two ApoE SNPs. Carriers of minor ESR2 alleles showed significantly reduced cognitive performance in the CERAD total score with most pronounced deficits in semantic memory (rs1256062, rs10144225, and rs2274705) and executive function (rs1256062). The minor allele effects of ESR2 were stronger in carriers of APOEε4 for the cognitive domain ‘executive function’ (p value of interaction 0.023 for rs1256062). The investigated ESR1 SNPs were not associated with cognition. Furthermore, we found a significant gene–environment interaction between the ESR2 SNP rs1256062 and air pollution on cognition. Carriers of two major alleles of rs1256062 were more susceptible for an air pollution-induced decrease in performance of ‘figure copying’ than carriers of minor alleles (p value of interaction, e.g., 0.031 for PM_2.5). In conclusion, ESR2 but not ESR1 minor alleles were associated with lower cognitive performance in elderly women with an indication of a gene–gene interaction with APOEε4. We also found indications for gene–environment interactions of ESR2 with traffic-related air pollution exposure on cognitive performance.

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Title: Estrogen receptor beta polymorphisms and cognitive performance in women: associations and modifications by genetic and environmental influences
Authors: Karin Fehsel
Tamara Schikowski
Michaela Jänner
Anke Hüls
Mohammed Voussoughi
Thomas Schulte
Andrea Vierkötter
Tom Teichert
Christian Herder
Dorothea Sugiri
Ursula Krämer
Christian Luckhaus
Publication date: 01-12-2016
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 12/2016
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-016-1620-8

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Estrogen receptor beta polymorphisms and cognitive performance in women: associations and modifications by genetic and environmental influences

Abstract

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