Functional polymorphisms of the mineralocorticoid receptor gene NR3C2 are associated with diminished memory decline: Results from a longitudinal general-population study.
NR3C2 gene
cognitive decline
mineralocorticoid receptor
rs2070951
rs5522
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
26
03
2020
revised:
13
05
2020
accepted:
19
05
2020
pubmed:
20
6
2020
medline:
21
5
2021
entrez:
20
6
2020
Statut:
ppublish
Résumé
The mineralocorticoid receptor (MR) in the brain has a key role in the regulation of the central stress response and is associated with memory performance. We investigated whether the genetic polymorphisms rs5522 and rs2070951 of NR3C2 showed main and interactive effects with childhood trauma on memory decline. Declarative memory was longitudinally assessed in 1,318 participants from the community-dwelling Study of Health in Pomerania using the Verbal Learning and Memory Test (VLMT). In a subsample of 377 participants aged 60 and older, the Mini-Mental Status Examination (MMSE) was additionally applied. Mean follow-up time for the VLMT and MMSE were 6.4 and 10.7 years, respectively. Homozygous carriers of the G allele of rs2070951 (p < .01) and of the A allele of rs5522 (p < .001) showed higher immediate recall of words as compared to carriers of C allele (rs2070951) or the G allele (rs5522). The CG haplotype was associated with decreased recall (p < .001). Likewise, in the subsample of older patients, the AA genotype of rs5522 was associated with higher MMSE scores (p < .05). CG haplotypes showed significantly reduced MMSE scores in comparison to the reference haplotype (β = -0.60; p < .01). Our results indicate that the GG genotype of rs2070951 as well as the AA genotype of rs5522 are associated with diminished memory decline.
Sections du résumé
BACKGROUND
The mineralocorticoid receptor (MR) in the brain has a key role in the regulation of the central stress response and is associated with memory performance. We investigated whether the genetic polymorphisms rs5522 and rs2070951 of NR3C2 showed main and interactive effects with childhood trauma on memory decline.
METHODS
Declarative memory was longitudinally assessed in 1,318 participants from the community-dwelling Study of Health in Pomerania using the Verbal Learning and Memory Test (VLMT). In a subsample of 377 participants aged 60 and older, the Mini-Mental Status Examination (MMSE) was additionally applied. Mean follow-up time for the VLMT and MMSE were 6.4 and 10.7 years, respectively.
RESULTS
Homozygous carriers of the G allele of rs2070951 (p < .01) and of the A allele of rs5522 (p < .001) showed higher immediate recall of words as compared to carriers of C allele (rs2070951) or the G allele (rs5522). The CG haplotype was associated with decreased recall (p < .001). Likewise, in the subsample of older patients, the AA genotype of rs5522 was associated with higher MMSE scores (p < .05). CG haplotypes showed significantly reduced MMSE scores in comparison to the reference haplotype (β = -0.60; p < .01).
CONCLUSIONS
Our results indicate that the GG genotype of rs2070951 as well as the AA genotype of rs5522 are associated with diminished memory decline.
Identifiants
pubmed: 32558353
doi: 10.1002/mgg3.1345
pmc: PMC7507013
doi:
Substances chimiques
NR3C2 protein, human
0
Receptors, Mineralocorticoid
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1345Informations de copyright
© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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