Interaction of insulin and PPAR-α genes in Alzheimer's disease: The Epistasis Project

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

doi:10.1007/s00702-011-0732-4

Interaction of insulin and PPAR-α genes in Alzheimer's disease: The Epistasis Project

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 MateoWolfgang Maier, Kevin Morgan, Donald R. Warden, A. David Smith, Reinhard Heun

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	473-479
Number of pages	7
Journal	Journal of Neural Transmission
Volume	119
Issue number	4
DOIs	https://doi.org/10.1007/s00702-011-0732-4
Publication status	Published - Apr 2012

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Kölsch, H., Lehmann, D. J., Ibrahim-Verbaas, C. A., Combarros, O., Van Duijn, C. M., Hammond, N., Belbin, O., Cortina-Borja, M., Lehmann, M. G., Aulchenko, Y. S., Schuur, M., Breteler, M., Wilcock, G. K., Brown, K., Kehoe, P. G., Barber, R., Coto, E., Alvarez, V., Deloukas, P., ... Heun, R. (2012). Interaction of insulin and PPAR-α genes in Alzheimer's disease: The Epistasis Project. Journal of Neural Transmission, 119(4), 473-479. https://doi.org/10.1007/s00702-011-0732-4

@article{e00fe4ba9d6c45fa83cc4d6a23861e28,

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.",

keywords = "Alzheimer's disease, Glucose metabolism, Heterosis, Insulin, Peroxisome proliferator-activated receptor alpha",

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

year = "2012",

month = apr,

doi = "10.1007/s00702-011-0732-4",

language = "English",

volume = "119",

pages = "473--479",

journal = "Journal of Neural Transmission",

issn = "0300-9564",

publisher = "Springer Verlag",

number = "4",

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Kölsch, H, Lehmann, DJ, Ibrahim-Verbaas, CA, Combarros, O, Van Duijn, CM, Hammond, N, Belbin, O, Cortina-Borja, M, Lehmann, MG, Aulchenko, YS, Schuur, M, Breteler, M, Wilcock, GK, Brown, K, Kehoe, PG, Barber, R, Coto, E, Alvarez, V, Deloukas, P, Mateo, I, Maier, W, Morgan, K, Warden, DR, Smith, AD & Heun, R 2012, 'Interaction of insulin and PPAR-α genes in Alzheimer's disease: The Epistasis Project', Journal of Neural Transmission, vol. 119, no. 4, pp. 473-479. https://doi.org/10.1007/s00702-011-0732-4

TY - JOUR

T1 - Interaction of insulin and PPAR-α genes in Alzheimer's disease

T2 - The Epistasis Project

AU - Kölsch, Heike

AU - Lehmann, Donald J.

AU - Ibrahim-Verbaas, Carla A.

AU - Combarros, Onofre

AU - Van Duijn, Cornelia M.

AU - Hammond, Naomi

AU - Belbin, Olivia

AU - Cortina-Borja, Mario

AU - Lehmann, Michael G.

AU - Aulchenko, Yurii S.

AU - Schuur, Maaike

AU - Breteler, Monique

AU - Wilcock, Gordon K.

AU - Brown, Kristelle

AU - Kehoe, Patrick G.

AU - Barber, Rachel

AU - Coto, Eliecer

AU - Alvarez, Victoria

AU - Deloukas, Panos

AU - Mateo, Ignacio

AU - Maier, Wolfgang

AU - Morgan, Kevin

AU - Warden, Donald R.

AU - Smith, A. David

AU - Heun, Reinhard

PY - 2012/4

Y1 - 2012/4

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Glucose metabolism

KW - Heterosis

KW - Insulin

KW - Peroxisome proliferator-activated receptor alpha

UR - http://www.scopus.com/inward/record.url?scp=84863450316&partnerID=8YFLogxK

U2 - 10.1007/s00702-011-0732-4

DO - 10.1007/s00702-011-0732-4

M3 - Article

C2 - 22065208

AN - SCOPUS:84863450316

VL - 119

SP - 473

EP - 479

JO - Journal of Neural Transmission

JF - Journal of Neural Transmission

SN - 0300-9564

IS - 4

ER -

Interaction of insulin and PPAR-α genes in Alzheimer's disease: The Epistasis Project

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