title: Interaction of insulin and PPAR-α genes in Alzheimer's disease: the Epistasis Project.
abstract: 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.
authors: Department of Psychiatry, University of Bonn, Bonn, Germany. heike.koelsch@uni-bonn.de
authors: Heike
authors: H
authors: Kölsch
authors: Donald J
authors: DJ
authors: Lehmann
authors: Carla A
authors: CA
authors: Ibrahim-Verbaas
authors: Onofre
authors: O
authors: Combarros
authors: Cornelia M
authors: CM
authors: van Duijn
authors: Naomi
authors: N
authors: Hammond
authors: Olivia
authors: O
authors: Belbin
authors: Mario
authors: M
authors: Cortina-Borja
authors: Michael G
authors: MG
authors: Lehmann
authors: Yurii S
authors: YS
authors: Aulchenko
authors: Maaike
authors: M
authors: Schuur
authors: Monique
authors: M
authors: Breteler
authors: Gordon K
authors: GK
authors: Wilcock
authors: Kristelle
authors: K
authors: Brown
authors: Patrick G
authors: PG
authors: Kehoe
authors: Rachel
authors: R
authors: Barber
authors: Eliecer
authors: E
authors: Coto
authors: Victoria
authors: V
authors: Alvarez
authors: Panos
authors: P
authors: Deloukas
authors: Ignacio
authors: I
authors: Mateo
authors: Wolfgang
authors: W
authors: Maier
authors: Kevin
authors: K
authors: Morgan
authors: Donald R
authors: DR
authors: Warden
authors: A David
authors: AD
authors: Smith
authors: Reinhard
authors: R
authors: Heun
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D004843:Epistasis, Genetic; D005060:Europe; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000235:genetics*; D008297:Male; D047493:PPAR alpha / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D053327:Apolipoprotein E4; D007328:Insulin; D047493:PPAR alpha