Paraoxonase 1 polymorphisms In Alzheimer's disease, Parkinson's disease, and AD-PD spectrum diseases

• Type of Material: Article
• Authors: Thomas S. Wingo, Emory University; Ami Rosen, Emory University; David J Cutler, Emory University; James J Lah, Emory University; Allan I Levey, Emory University
• Language: English
• Date: 2012-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012, Elsevier
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.neurobiolaging.2010.08.010
• Title of Journal or Parent Work: Neurobiology of Aging
• ISSN: 0197-4580
• Volume: 33
• Issue: 1
• Start Page: 204.e13
• End Page: 204.e15
• Grant/Funding Information: This work was supported by the Emory Alzheimer's Disease Research Center Grant AG025688 and Emory NINDS Neuroscience Core Facilities Grant NS055077.
• Research Categories: Biology, Genetics; Gerontology; Biology, Neuroscience

Abstract

Paraoxonase 1 (PON1) is a serum arylsulfatase that metabolizes organophosphate pesticides and protects low-density lipoprotein from oxidation. Case-control studies of PON1 genetic variants in Alzheimer's disease (AD) and Parkinson's disease (PD) have revealed some positive albeit inconsistent associations with two PON1-coding polymorphisms: Q192R (rs662) and L55M (rs854560). Because AD and PD exist along a spectrum of disorders with shared epidemiologic, clinical, and pathologic features, here we evaluated PON1 variants in a cohort of 746 AD, 566 PD, 132 AD-PD, and 719 cognitively normal age-matched controls. In the combined AD and Caucasian PD cohorts we had 80% power to detect a relative risk of at least 1.25 and 1.35, respectively, for each polymorphism. We found no association between two PON1 coding polymorphisms and AD in African Americans or Caucasians, and no association with PD or AD-PD in Caucasians. There was also no evidence of an interaction between PON1 and apolipoprotein E for any of these diseases. Our results suggest that either these functional PON1 polymorphisms are not associated with AD and PD spectrum disorders, or that the relative risk conferred is small.