| Serum paraoxonase activity is associated with variants in the PON gene cluster and risk of Alzheimer disease. | |
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MedLine Citation:
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PMID: 20980077 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-10-27 |
Journal Detail:
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Title: Neurobiology of aging Volume: 33 ISSN: 1558-1497 ISO Abbreviation: Neurobiol. Aging Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-03-19 Completed Date: 2012-11-23 Revised Date: 2013-05-27 |
Medline Journal Info:
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Nlm Unique ID: 8100437 Medline TA: Neurobiol Aging Country: United States |
Other Details:
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Languages: eng Pagination: 1015.e7-23 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Medicine (Genetics Program), Boston University School of Medicine, Boston, MA 02118, USA. farrer@bu.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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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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