Influence of PCSK9 polymorphisms on plasma lipids and response to atorvastatin treatment in Brazilian subjects

被引：25

作者：

Anderson, Jacqueline M. ^{[1
]}

Cerda, Alvaro ^{[1
,2
]}

Hirata, Mario H. ^{[1
]}

Rodrigues, Alice C. ^{[3
]}

Dorea, Egidio L. ^{[4
]}

Bernik, Marcia M. S. ^{[4
]}

Bertolami, Marcelo C. ^{[5
]}

Faludi, Andre A. ^{[5
]}

Hirata, Rosario D. C. ^{[1
]}

机构：

[1] Univ Sao Paulo, Sch Pharmaceut Sci, BR-05508000 Sao Paulo, Brazil

[2] Univ La Frontera, Ctr Mol Biol & Pharmacogenet, Sci & Technol Bioresource Nucleus, Temuco, Chile

[3] Univ Sao Paulo, Inst Biomed Sci, BR-05508000 Sao Paulo, Brazil

[4] Univ Sao Paulo, Univ Hosp, BR-05508000 Sao Paulo, Brazil

[5] Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil

来源：

JOURNAL OF CLINICAL LIPIDOLOGY | 2014年 / 8卷 / 03期

基金：

巴西圣保罗研究基金会;

关键词：

Proprotein convertase subtilisin/kexin type 9 (PCSK9); Single nucleotide polymorphism; Cholesterol; Atorvastatin; Pharmacogenomics; LIPOPROTEIN CHOLESTEROL LEVELS; C-TERMINAL DOMAIN; GENETIC-VARIANTS; STATINS; RISK; DISEASE; HYPERCHOLESTEROLEMIA; PHARMACOGENETICS; ATHEROSCLEROSIS; DYSLIPIDEMIA;

D O I：

10.1016/j.jacl.2014.02.008

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

BACKGROUND: The proprotein convertase subtilisin/kexin type 9 (PCSK9) has a key role in the regulation of plasma low-density lipoprotein (LDL) cholesterol by enhancing the degradation of LDL receptor. Functional variants in PCSK9 have been associated with differences in plasma lipids and may contribute to the variability of the response to cholesterol-lowering drugs. OBJECTIVE: To investigate the influence of PCSK9 variants on plasma lipid profile and response to atorvastatin in Brazilian subjects. METHODS: PCSK9 E670G, 1474V, and R46L single nucleotide polymorphisms (SNPs) and plasma lipids were evaluated in 163 hypercholesterolemics (HC) and 171 normolipidemics (NL). HC patients with indication for cholesterol-lowering drug therapy (n = 128) were treated with atorvastatin (10 mg/d/4 wk). PCSK9 SNPs were analyzed by real time polymerase chain reaction. RESULTS: Frequencies of the PCSK9 SNPs were similar between the HC and NL groups. Logistic regression analysis showed a trend of association between PCSK9 E670G and hypercholesterolemia after adjustment for covariates (P = .059). The 670G allele was associated with high basal levels of LDL cholesterol (P = .03) in HC patients using the extreme discordant phenotype method. No association tests were performed for R46L variant because of its very low frequency, whereas the 1474V polymorphism and PCSK9 haplotypes were not related to hypercholesterolemia or variability on plasma lipids in both NL and HC groups (P > .05). LDL cholesterol reduction in response to atorvastatin was not influenced by PCSK9 genotypes or haplotypes. CONCLUSIONS: PCSK9 E670G polymorphism but not 1474V contributes to the variability on plasma LDL cholesterol levels in hypercholesterolemic subjects. Both PCSK9 variants have no influence on cholesterol-lowering response to atorvastatin. (C) 2014 National Lipid Association. All rights reserved.

引用

页码：256 / 264

页数：9

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