Document Detail


PCSK9 SNP rs11591147 is associated with low cholesterol levels but not with cognitive performance or noncardiovascular clinical events in an elderly population.
MedLine Citation:
PMID:  23300213     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Proprotein convertase subtilisin-like/kexin type 9 (PCSK9) is a protein involved in LDL-cholesterol metabolism. The single-nucleotide polymorphism (SNP) rs11591147 has been associated with lower LDL-cholesterol and a lower risk of coronary heart disease. Because PCSK9 has high affinity to the LDL receptor, inhibiting PCSK9 is a testable therapeutic target for lipid-lowering therapy. Currently, several approaches to inhibit PCSK9 are under development, but it is unknown what the effects of those inhibitors will be on cognition or noncardiovascular clinical events. In this study, we assessed the association between rs11591147 and cognitive performance, activities of daily living (ADL), and noncardiovascular clinical events within 5,777 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Rs11591147 was associated with 10% to 16% lower LDL cholesterol levels (P = 3.62 × 10(-12)), but was not associated with cognitive performance, ADL, or noncardiovascular clinical events in the PROSPER study. Our findings suggest that lower cholesterol levels due to genetic variation in the PCSK9 gene are not associated with cognitive performance, functional status, or noncardiovascular clinical events.
Authors:
Iris Postmus; Stella Trompet; Anton J M de Craen; Brendan M Buckley; Ian Ford; David J Stott; Naveed Sattar; P Eline Slagboom; Rudi G J Westendorp; J Wouter Jukema
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of lipid research     Volume:  54     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-09     Completed Date:  2013-06-05     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  561-6     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Activities of Daily Living
Aged
Cholesterol, LDL / blood*
Cognition* / drug effects
Female
Follow-Up Studies
Humans
Male
Polymorphism, Single Nucleotide*
Pravastatin / pharmacology
Proprotein Convertases / genetics*
Serine Endopeptidases / genetics*
Vascular Diseases / blood,  genetics,  physiopathology,  prevention & control
Chemical
Reg. No./Substance:
0/Cholesterol, LDL; EC 3.4.-/Proprotein Convertases; EC 3.4.21.-/PCSK9 protein, human; EC 3.4.21.-/Serine Endopeptidases; KXO2KT9N0G/Pravastatin
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