The human SMAD9 (GCC) repeat links to natural selection and late-onset neurocognitive disorders.
(GCC) repeat
Alzheimer’s disease
Late-onset neurocognitive disorder
Natural selection
SMAD9
Vascular dementia
Journal
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
ISSN: 1590-3478
Titre abrégé: Neurol Sci
Pays: Italy
ID NLM: 100959175
Informations de publication
Date de publication:
14 Jun 2024
14 Jun 2024
Historique:
received:
20
09
2023
accepted:
05
06
2024
medline:
15
6
2024
pubmed:
15
6
2024
entrez:
14
6
2024
Statut:
aheadofprint
Résumé
Whereas (GCC)-repeats are overrepresented in genic regions, and mutation hotspots, they are largely unexplored with regard to their link with natural selection. Across numerous primate species and tissues, SMAD9 (SMAD Family Member 9) reaches highest level of expression in the human brain. This gene contains a (GCC)-repeat in the interval between + 1 and + 60 of the transcription start site, which is in the high-ranking (GCC)-repeats with respect to length. Here we sequenced this (GCC)-repeat in 396 Iranian individuals, consisting of late-onset neurocognitive disorder (NCD) (N = 181) and controls (N = 215). We detected two predominantly abundant alleles of 7 and 9 repeats, forming 96.2% of the allele pool. The (GCC)7/(GCC)9 ratio was in the reverse order in the NCD group versus controls (p = 0.005), resulting from excess of (GCC)7 in the NCD group (p = 0.003) and (GCC)9 in the controls (p = 0.01). Five genotypes, predominantly consisting of (GCC)7 and lacking (GCC)9 were detected in the NCD group only (p = 0.008). The patients harboring those genotypes received the diagnoses of Alzheimer's disease (AD) and vascular dementia (VD). Five genotypes consisting of (GCC)9 and lacking (GCC)7 were detected in the control group only (p = 0.002). The group-specific genotypes formed approximately 4% of the genotype pool in the human samples studied. We propose natural selection and a novel locus for late-onset AD and VD at the SMAD9 (GCC)-repeat in humans.
Identifiants
pubmed: 38877206
doi: 10.1007/s10072-024-07637-y
pii: 10.1007/s10072-024-07637-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. Fondazione Società Italiana di Neurologia.
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