Document Detail


Serum paraoxonase activity is associated with variants in the PON gene cluster and risk of Alzheimer disease.
MedLine Citation:
PMID:  20980077     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previous studies have shown association of single nucleotide polymorphisms (SNPs) in 3 contiguous genes (PON1, PON2, and PON3) encoding paraoxonase with risk of Alzheimer disease (AD). We evaluated the association of serum paraoxonase activity measured by phenyl acetate (PA) and thiobutyl butyrolactone (TBBL) with risk of AD and with 26 SNPs spanning the PON gene cluster in 266 AD cases and 306 sibling controls from the MIRAGE study. The odds of AD (adjusted for age, gender, and ethnicity) increased 20% for each standard deviation decrease in PA or TBBL activity. There were association signals with activity in all 3 genes. Haplotypes including SNPs spanning the PON genes were generally more significant than haplotypes comprising SNPs from 1 gene. Significant interactions were observed between SNP pairs located across the PON cluster with either serum activity measure as the outcome, and between several PON SNPs and PA activity with AD status as the outcome. Our results suggest that low serum paraoxonase activity is a risk factor for AD. Furthermore, multiple variants in PON influence serum paraoxonase activity and their effects may be synergistic.
Authors:
Porat M Erlich; Kathryn L Lunetta; L Adrienne Cupples; Carmela R Abraham; Robert C Green; Clinton T Baldwin; Lindsay A Farrer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-10-27
Journal Detail:
Title:  Neurobiology of aging     Volume:  33     ISSN:  1558-1497     ISO Abbreviation:  Neurobiol. Aging     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-03-19     Completed Date:  2012-11-23     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  8100437     Medline TA:  Neurobiol Aging     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1015.e7-23     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Department of Medicine (Genetics Program), Boston University School of Medicine, Boston, MA 02118, USA. farrer@bu.edu
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Alzheimer Disease / enzymology*,  epidemiology,  genetics*
Aryldialkylphosphatase / blood*,  deficiency,  genetics*,  physiology
Drug Synergism
Female
Genetic Predisposition to Disease / epidemiology,  genetics*
Genetic Variation*
Humans
Male
Multigene Family / genetics*
Polymorphism, Single Nucleotide / genetics*
Risk Factors
Grant Support
ID/Acronym/Agency:
K24-AG027841/AG/NIA NIH HHS; P30 AG013846/AG/NIA NIH HHS; P30 AG013846-13/AG/NIA NIH HHS; P30-AG13846/AG/NIA NIH HHS; R01 AG009029-15/AG/NIA NIH HHS; R01 AG025259-05/AG/NIA NIH HHS; R01-AG025259/AG/NIA NIH HHS; R01-AG09029/AG/NIA NIH HHS; R01-HG/AG02213/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
EC 3.1.8.1/Aryldialkylphosphatase; EC 3.1.8.1/PON1 protein, human; EC 3.1.8.1/PON2 protein, human; EC 3.1.8.1/PON3 protein, human
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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