title: PCSK9 SNP rs11591147 is associated with low cholesterol levels but not with cognitive performance or noncardiovascular clinical events in an elderly population.
abstract: 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.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. i.postmus@lumc.nl
authors.forename: Iris
authors.initials: I
authors.lastname: Postmus
authors.forename: Stella
authors.initials: S
authors.lastname: Trompet
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Buckley
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.forename: David J
authors.initials: DJ
authors.lastname: Stott
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D008078:Cholesterol, LDL / Q000097:blood*; D003071:Cognition / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017035:Pravastatin / Q000494:pharmacology; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*; D014652:Vascular Diseases / Q000097:blood / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D008078:Cholesterol, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D017035:Pravastatin