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

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP ANDERSON, Jacqueline M.
CERDA, Alvaro
HIRATA, Mario H.
BERNIK, Marcia M. S.
FALUDI, Andre A.
HIRATA, Rosario D. C. 2014
dc.identifier.citation JOURNAL OF CLINICAL LIPIDOLOGY, v.8, n.3, p.256-264, 2014
dc.identifier.issn 1933-2874
dc.description.abstract 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.
dc.description.sponsorship · Sao Paulo Research Foundation (FAPESP) [2008-06667-9]
· Sao Paulo, Brazil
· National Council for Research and Development (CNPq), Brasilia, Brazil
· CNPq
· CONICYT, Chile
dc.language.iso eng
dc.relation.ispartof Journal of Clinical Lipidology
dc.rights restrictedAccess
dc.subject Proprotein convertase subtilisin/kexin type 9 (PCSK9); Single nucleotide polymorphism; Cholesterol; Atorvastatin; Pharmacogenomics
dc.subject.other density-lipoprotein cholesterol; c-terminal domain; genetic-variants; statin therapy; population; risk; hypercholesterolemia; atherosclerosis; degradation; receptor
dc.title Influence of PCSK9 polymorphisms on plasma lipids and response to atorvastatin treatment in Brazilian subjects
dc.type article
dc.rights.holder Copyright ELSEVIER SCIENCE INC
dc.identifier.doi 10.1016/j.jacl.2014.02.008
dc.identifier.pmid 24793346
dc.type.category original article
dc.type.version publishedVersion DOREA, Egidio L.:HU:DVCLME-62 · ANDERSON, Jacqueline M.:Univ Sao Paulo, Sch Pharmaceut Sci, BR-05508000 Sao Paulo, Brazil
· CERDA, Alvaro:Univ Sao Paulo, Sch Pharmaceut Sci, BR-05508000 Sao Paulo, Brazil; Univ La Frontera, Ctr Mol Biol & Pharmacogenet, Sci & Technol Bioresource Nucleus, Temuco, Chile
· HIRATA, Mario H.:Univ Sao Paulo, Sch Pharmaceut Sci, BR-05508000 Sao Paulo, Brazil
· RODRIGUES, Alice C.:Univ Sao Paulo, Inst Biomed Sci, BR-05508000 Sao Paulo, Brazil
· BERNIK, Marcia M. S.:Univ Sao Paulo, Univ Hosp, BR-05508000 Sao Paulo, Brazil
· BERTOLAMI, Marcelo C.:Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil
· FALUDI, Andre A.:Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil
· HIRATA, Rosario D. C.:Univ Sao Paulo, Sch Pharmaceut Sci, BR-05508000 Sao Paulo, Brazil WOS:000335284200004 2-s2.0-84899711770 NEW YORK USA
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dc.description.index MEDLINE
dc.identifier.eissn 1876-4789
hcfmusp.citation.scopus 15
hcfmusp.citation.wos 13 Brasil Chile

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