Candidate gene association study of insulin signaling genes and Alzheimer's disease: evidence for SOS2, PCK1, and PPARgamma as susceptibility loci.
Epidemiological evidence supports the existence of a possible link between type II diabetes mellitus (T2DM) and late-onset Alzheimer's disease (LOAD). Polymorphisms from candidate genes for T2DM were genotyped in a two-stage approach to identify novel risk factors for LOAD. One hundred fifty-two polymorphisms were initially genotyped in a case:control cohort: nine SNPs showed individual association with disease status under at least one genetic model, while an additional two SNPs showed a haplotype association. In a replication study, we confirmed significant association of SNPs within three genes--PPARgamma, SOS2, and PCK1--with Alzheimer's disease. In particular, our data suggest that the effect of variants within these genes might be influenced by gender.
Hamilton
Gillian
G
MRC Centre for Neurodegeneration Research, Department of Neuroscience, Institute of Psychiatry, Kings College London, Denmark Hill, London, UK. G.Hamilton@iop.kcl.ac.uk
Proitsi
Petra
P
Jehu
Luke
L
Morgan
Angharad
A
Williams
Julie
J
O'Donovan
Michael C
MC
Owen
Michael J
MJ
Powell
John F
JF
Lovestone
Simon
S
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007328:Insulin / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D047495:PPAR gamma / Q000235:genetics*; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015221:Potassium Channels / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D011955:Receptors, Drug / Q000235:genetics; D012727:Sex Characteristics; D015398:Signal Transduction / Q000235:genetics*; D020664:Son of Sevenless Proteins / Q000235:genetics*; D064233:Sulfonylurea Receptors; D006113:United Kingdom / Q000453:epidemiology
D018528:ATP-Binding Cassette Transporters; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D047495:PPAR gamma; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; C485509:SOS2 protein, human; D020664:Son of Sevenless Proteins; D064233:Sulfonylurea Receptors; C521898:PCK1 protein, human; D010729:Phosphoenolpyruvate Carboxykinase (GTP)