Interaction of insulin and PPAR-alpha genes in Alzheimer's disease: the Epistasis Project

H Kolsch, DJ Lehmann, Carla Verbaas, O Combarros, Cornelia Duijn, N Hammond, O Belbin, M Cortina-Borja, MG Lehmann, YS Aulchenko, Maaike Schuur, Monique Breteler, GK Wilcock, K Brown, PG Kehoe, R Barber, E Coto, V Alvarez, P Deloukas, I MateoW Maier, K Morgan, DR Warden, AD Smith, R Heun

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Altered glucose metabolism has been described in Alzheimer's disease (AD). We re-investigated the interaction of the insulin (INS) and the peroxisome proliferator-activated receptor alpha (PPARA) genes in AD risk in the Epistasis Project, including 1,757 AD cases and 6,294 controls. Allele frequencies of both SNPs (PPARA L162V, INS intron 0 A/T) differed between Northern Europeans and Northern Spanish. The PPARA 162LL genotype increased AD risk in Northern Europeans (p = 0.04), but not in Northern Spanish (p = 0.2). There was no association of the INS intron 0 TT genotype with AD. We observed an interaction on AD risk between PPARA 162LL and INS intron 0 TT genotypes in Northern Europeans (Synergy factor 2.5, p = 0.016), but not in Northern Spanish. We suggest that dysregulation of glucose metabolism contributes to the development of AD and might be due in part to genetic variations in INS and PPARA and their interaction especially in Northern Europeans.
Original languageUndefined/Unknown
Pages (from-to)473-479
Number of pages7
JournalJournal of Neural Transmission
Issue number4
Publication statusPublished - 2012

Research programs

  • EMC COEUR-09
  • EMC NIHES-01-64-02

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