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Genetic variation at the PCSK9 locus moderately lowers low-density lipoprotein cholesterol levels, but does not significantly lower vascular disease risk in an elderly population.

Abstract：

:Caucasian carriers of the T allele at R46L in the proprotein convertase subtilisin/kexin type 9 (PCSK9) locus have been reported to have 15% lower low-density lipoprotein (LDL) cholesterol (C) levels and 47% lower coronary heart disease (CHD) risk. Our objective was to examine two PCSK9 single nucleotide polymorphisms (SNPs), R46L and E670G, in 5783 elderly participants in Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), of whom 43% had a history of vascular disease at baseline, and who were randomized to pravastatin or placebo with followup. In this population 3.5% were carriers of the T allele at R46L, and these subjects had significantly (p<0.001) lower levels of LDL C (mean, -10%), no difference in LDL C lowering response to pravastatin, and a non-significant 19% unadjusted and 9% adjusted decreased risk of vascular disease at baseline, with no on trial effect. Moreover, 6.0% were carriers of the G allele at E670G with no significant relationships with baseline LDL C, response to pravastatin, or vascular disease risk being observed. Our data support the concept that the rare allele of the R46L SNP at the PCSK9 locus significantly lowers LDL C, but does not greatly reduce CHD risk in an elderly population with a high prevalence of cardiovascular disease.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Polisecki E,Peter I,Robertson M,McMahon AD,Ford I,Packard C,Shepherd J,Jukema JW,Blauw GJ,Westendorp RG,de Craen AJ,Trompet S,Buckley BM,Murphy MB,Ordovas JM,Schaefer EJ,PROSPER Study Group.

doi

10.1016/j.atherosclerosis.2007.12.005

subject

Has Abstract

pub_date

2008-09-01 00:00:00

pages

95-101

issue

1

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(07)00793-9

journal_volume

200

pub_type

杂志文章,随机对照试验

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