Gene-environment Interaction Between Estrogen Receptor (ER) SS, ApoE and Air Pollution On Cognitive Performance in an Elderly, Female Cohort.

Abstract

Introduction In the brain, estrogen plays an important role in neural plasticity and its decline during menopause might result in cognitive impairment and predispose to the development of dementia. Two estrogen receptors – α and s – mediate estrogen actions either as ligand-activated dimeric transcription factors or as membrane-embedded ER monomers. Objective To analyze ERs-variants and ApoE-genotype in the population-based SALIA cohort of 834 non-demented, elderly women. Aims We aimed to explore, whether ERs variants may impact on cognitive performance in interaction with air pollution and APOE. Methods DNA was isolated from lymphocytes. ApoE-epsilon-variants and ERs SNPs rs944045, rs1256062, rs10144225 and rs2274705 were determined by LCG /KBioscience (Hoddesdon, UK). All participants were assessed for cognitive impairment by the CERAD-Plus test battery. Subtests were merged to a total z-score, that corrected for gender, age and time of education. Long-term exposure to air pollution was backextrapolated from data collected by monitoring stations using a geographic information system. Results SNP analysis revealed that 3 ERs variants (rs1256062, rs10144225 and rs2274705) were significantly correlated with lower CERAD z total scores and especially with decline in episodic memory. These effects were strengthened in APOE-epsilon-E4 carriers. Air pollution (NO2, PM2,5) did not worsen the CERAD z total score of the women, but interacting with the ERs variants PM2,5 affected their visuoconstructive practice and NO2 their semantic memory. Conclusion In this population-based, prospective study a gene-gene interaction effect of ApoE and ERs on cognitive performance appeared. Moreover, significant gene-environment interactions on cognition were found for air pollution.