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.

Authors: Erickson RP; Larson-Thomé K; Weberg L; Szybinska A; Mossakowska M; Styczynska M; Barcikowska M; Kuznicki J

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.

Keywords: Aged; Aged, 80 and over; Aging/*genetics; Alzheimer Disease/*genetics; Carrier Proteins/*genetics; Chi-Square Distribution; Female; Gene Frequency; Genotype; Humans; Male; Membrane Glycoproteins/*genetics; Poland; Polymorphism, Single Nucleotide/*genetics
Journal: Neuroscience letters
Volume: 447
Issue: 2-3
Pages: 153-7
Date: Oct. 7, 2008
PMID: 18834923
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Citation:

Erickson RP, Larson-Thomé K, Weberg L, Szybinska A, Mossakowska M, Styczynska M, Barcikowska M, Kuznicki J (2008) 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. Neuroscience letters 447: 153-7.


Longevity Variant Associations (p-value):
  • rs1805081 (0.007)
  • rs1631685 (0.026)
  • rs1788799

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