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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Acknowledgments
We are most grateful to the Moulton Charitable Foundation for a grant to fund the Epistasis Project, to all those who have provided support for the individual clinical studies and to the Alzheimer’s Research Trust. GKW was partly funded by the NIHR Biomedical Research Centre Programme, Oxford.
Conflict of interest
Professor Maier received research grants from the following companies, respectively, is member of the Advisory Boards or draws a fee for speech from: AstraZeneca, Bayer Vital, Böhringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, General Electrics, Janssen-Cilag, Lundbeck, Merck, Merz, Novartis, Pfizer, Sanofi-Aventis, Schering. The other authors declare that they have no competing interests.
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Kölsch, H., Lehmann, D.J., Ibrahim-Verbaas, C.A. et al. Interaction of insulin and PPAR-α genes in Alzheimer’s disease: the Epistasis Project. J Neural Transm 119, 473–479 (2012). https://doi.org/10.1007/s00702-011-0732-4
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DOI: https://doi.org/10.1007/s00702-011-0732-4