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

  • Translational Neurosciences - Original Article
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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 PM2.5). 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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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich Heine University Düsseldorf, Bergische Landstrasse 2, 40629, Düsseldorf, Germany

    Karin Fehsel, Michaela Jänner, Thomas Schulte & Christian Luckhaus

  2. IUF - Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Germany

    Tamara Schikowski, Anke Hüls, Mohammed Voussoughi, Andrea Vierkötter, Dorothea Sugiri & Ursula Krämer

  3. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany

    Tom Teichert & Christian Herder

  4. German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Germany

    Tom Teichert & Christian Herder

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  1. Karin Fehsel
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  2. Tamara Schikowski
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  3. Michaela Jänner
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  4. Anke Hüls
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  5. Mohammed Voussoughi
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  6. Thomas Schulte
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  7. Andrea Vierkötter
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  8. Tom Teichert
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  9. Christian Herder
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  10. Dorothea Sugiri
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  11. Ursula Krämer
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  12. Christian Luckhaus
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Correspondence to Karin Fehsel.

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Funding

This study was supported by research grants from the Deutsche Forschungsgemeinschaft (DFG; HE-4510/2-1, KR 1938/3-1, LU 691/4-1). The 22-year SALIA follow-up study was funded by the German Statutory Accident Insurance (DGUV). The German Diabetes Center is funded by the German Federal Ministry of Health and the Ministry of School, Science and Research of the State of North-Rhine-Westphalia. This study was supported in part by a grant from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD e.V.). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of manuscript.

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Fehsel, K., Schikowski, T., Jänner, M. et al. Estrogen receptor beta polymorphisms and cognitive performance in women: associations and modifications by genetic and environmental influences. J Neural Transm 123, 1369–1379 (2016). https://doi.org/10.1007/s00702-016-1620-8

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