期刊
ATHEROSCLEROSIS
卷 200, 期 1, 页码 95-101出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2007.12.005
关键词
genetics; statins; low-density lipoproteins (LDL); coronary heart disease (CHD); proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9); vascular disease; elderly
资金
- NHLBI NIH HHS [R01 HL074753] Funding Source: Medline
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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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