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01-04-2012 | Dementias - Original Article

Interaction of insulin and PPAR-α genes in Alzheimer’s disease: the Epistasis Project

Authors: Heike Kölsch, Donald J. Lehmann, Carla A. Ibrahim-Verbaas, Onofre Combarros, Cornelia M. van Duijn, Naomi Hammond, Olivia Belbin, Mario Cortina-Borja, Michael G. Lehmann, Yurii S. Aulchenko, Maaike Schuur, Monique Breteler, Gordon K. Wilcock, Kristelle Brown, Patrick G. Kehoe, Rachel Barber, Eliecer Coto, Victoria Alvarez, Panos Deloukas, Ignacio Mateo, Wolfgang Maier, Kevin Morgan, Donald R. Warden, A. David Smith, Reinhard Heun

Published in: Journal of Neural Transmission | Issue 4/2012

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.

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Title: Interaction of insulin and PPAR-α genes in Alzheimer’s disease: the Epistasis Project
Authors: Heike Kölsch
Donald J. Lehmann
Carla A. Ibrahim-Verbaas
Onofre Combarros
Cornelia M. van Duijn
Naomi Hammond
Olivia Belbin
Mario Cortina-Borja
Michael G. Lehmann
Yurii S. Aulchenko
Maaike Schuur
Monique Breteler
Gordon K. Wilcock
Kristelle Brown
Patrick G. Kehoe
Rachel Barber
Eliecer Coto
Victoria Alvarez
Panos Deloukas
Ignacio Mateo
Wolfgang Maier
Kevin Morgan
Donald R. Warden
A. David Smith
Reinhard Heun
Publication date: 01-04-2012
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 4/2012
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-011-0732-4

At a glance: The STEP trials

Springer Medicine

Interaction of insulin and PPAR-α genes in Alzheimer’s disease: the Epistasis Project

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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