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Variation in PCSK9, low LDL cholesterol, and risk of peripheral arterial disease.

TitleVariation in PCSK9, low LDL cholesterol, and risk of peripheral arterial disease.
Publication TypeJournal Article
Year of Publication2009
AuthorsFolsom AR, Peacock JM, Boerwinkle E
Corporate AuthorsAtherosclerosis Risk in Communities(ARIC) Study Investigators
JournalAtherosclerosis
Volume202
Issue1
Pagination211-5
Date Published2009 Jan
ISSN1879-1484
KeywordsCholesterol, LDL, Cohort Studies, Ethnic Groups, Female, Genetic Predisposition to Disease, Genetic Variation, Humans, Male, Middle Aged, Peripheral Vascular Diseases, Prevalence, Proportional Hazards Models, Proprotein Convertase 9, Proprotein Convertases, Risk, Risk Factors, Serine Endopeptidases
Abstract

BACKGROUND: We hypothesized that variants in PCSK9 that lower LDL cholesterol levels are associated with reduced prevalence and incidence of peripheral artery disease (PAD).

METHODS: The Atherosclerosis Risk in Communities (ARIC) Study assessed risk factors and PCSK9 variants Y142X and C679X (relevant to blacks) and R46L (relevant to whites) in a cohort of 45-64-year olds in 1987-1989 (n=13,634). Prevalent PAD (n=619 cases) was defined by an ankle-brachial index

RESULTS: As expected, greater LDL cholesterol was a risk factor for prevalent and incident PAD. 2.4% of blacks and 3.1% of whites were carriers of one of the race-specific PCSK9 variants. Carriers had lower prevalence of PAD compared with non-carriers (2.3% vs. 4.6%). The corresponding age- and sex-adjusted odds ratio of PAD was 0.47 (95% confidence interval, 0.24-0.92). In contrast with the cross-sectional findings, there was no association between PCSK9 variants and incident PAD (age- and sex-adjusted hazard ratio, 1.09 (95% confidence interval, 0.76-1.57)).

CONCLUSIONS: Our study provides mixed evidence that variation in PCSK9 may contribute to genetic risk of PAD.

DOI10.1016/j.atherosclerosis.2008.03.009
Alternate JournalAtherosclerosis
PubMed ID18436227
PubMed Central IDPMC2607475
Grant ListN01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
N01 HC055019 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States