Variation in NPC1, the gene encoding Niemann-Pick C1, a protein involved in intracellular cholesterol transport, is associated with Alzheimer disease and/or aging in the Polish population.
Neurosci Lett
; 447(2-3): 153-7, 2008 Dec 12.
Article
em En
| MEDLINE
| ID: mdl-18834923
ABSTRACT
There is abundant evidence that cholesterol metabolism, especially as mediated by the intercellular transporter APOE, is involved in the pathogenesis of sporadic, late-onset Alzheimer disease (SLAD). Identification of other genes involved in SLAD pathogenesis has been hampered since gene association studies, whether individual or genome-wide, experience difficulty in finding appropriate controls in as much as 25% or more of normal adults will develop SLAD. Using 152 centenarians as additional controls and 120 "regular", 65-75-year-old controls, we show an association of genetic variation in NPC1 with SLAD and/or aging. In this preliminary study, we find gradients of two non-synonymous SNP's allele frequencies in NPC1 from centenarians through normal controls to SLAD in this non-stratified Polish population. An intervening intronic SNP is not in Hardy-Weinberg equilibria and differs between centenarians and controls/SLAD. Haplotypes frequencies determined by fastPHASE were somewhat different, and the predicted genotype frequencies were very different between the three groups. These findings can also be interpreted as indicating a role for NPC1 in aging, a role also suggested by NPC1's role in Dauer formation (hibernation, a longevity state) in Caenorhabditis elegans.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
/
Glicoproteínas de Membrana
/
Proteínas de Transporte
/
Polimorfismo de Nucleotídeo Único
/
Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
País/Região como assunto:
Europa
Idioma:
En
Revista:
Neurosci Lett
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos