Interaction of Insulin and PPAR-α Genes in Alzheimer's Disease: the Epistasis Project

Overview

Journal J Neural Transm (Vienna)

Specialties Neurology
Physiology

Date 2011 Nov 9

PMID 22065208

Citations 12

Authors

Heike Kolsch

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

Affiliations

Soon will be listed here.

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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