Neurobiology of Aging
Volume 33, Issue 1 , Pages 199.e13-199.e17, January 2012

Association between variants in IDE-KIF11-HHEX and plasma amyloid β levels

  • Christiane Reitz

      Affiliations

    • The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA
    • The Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA
    • Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
    • ,
  • Rong Cheng

      Affiliations

    • The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA
    • The Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA
    • Department of Epidemiology, School of Public Health, Columbia University, New York, NY, USA
    • ,
  • Nicole Schupf

      Affiliations

    • The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA
    • The Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA
    • Department of Epidemiology, School of Public Health, Columbia University, New York, NY, USA
    • ,
  • Joseph H. Lee

      Affiliations

    • The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA
    • The Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA
    • Department of Epidemiology, School of Public Health, Columbia University, New York, NY, USA
    • ,
  • Pankaj D. Mehta

      Affiliations

    • Department of Immunology, Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA
    • ,
  • Ekaterina Rogaeva

      Affiliations

    • Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada
    • ,
  • Peter St George-Hyslop

      Affiliations

    • Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada
    • Department of Medicine, University Health Network, Toronto, Ontario, Canada
    • Cambridge Institute for Medical Research and Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
    • ,
  • Richard Mayeux

      Affiliations

    • The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA
    • The Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA
    • Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
    • Department of Epidemiology, School of Public Health, Columbia University, New York, NY, USA
    • Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA
    • Corresponding Author InformationCorresponding author at: Gertrude H. Sergievsky Center, 630 West 168th Street, Columbia University, New York, NY 10032, USA. Tel.: +1 212 305 3192; fax: +1 212 305 2518

Received 7 April 2010; received in revised form 29 June 2010; accepted 5 July 2010. published online 19 August 2010.

Abstract 

Genetic linkage and association studies in late-onset Alzheimer’s disease (LOAD) or its endophenotypes have pointed to several regions on chromosome 10q, among these the ∼ 250 kb linkage disequilibrium (LD) block harboring the genes IDE, KIF1, and HHEX. We explored the association between variants in the genomic region harboring the IDE-KIF11-HHEX complex with plasma Aβ40 and Aβ42 levels in a case-control cohort of Caribbean Hispanics. First, we performed single marker linear regression analysis relating the individual single nucleotide polymorphisms (SNPs) with plasma Aβ40 and Aβ42 levels. Then we performed 3-SNP sliding window haplotype analyses, correcting all analyses for multiple testing. Out of 32 SNPs in this region, 3 SNPs in IDE (rs2421943, rs12264682, rs11187060) were associated with plasma Aβ40 or Aβ42 levels in single marker and haplotype analyses after correction for multiple testing. All these SNPs lie within the same LD block, and are in LD with the previously reported haplotypes. Our findings provide support for an association in the IDE region on chromosome 10q with Aβ40 and 42 levels.

Keywords: Amyloid beta, Alzheimer's disease, Genetics, Insulin-degrading enzyme

 

PII: S0197-4580(10)00312-X

doi:10.1016/j.neurobiolaging.2010.07.005

Neurobiology of Aging
Volume 33, Issue 1 , Pages 199.e13-199.e17, January 2012

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