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

Show simple item record

dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author ANDERSON, Jacqueline M.
CERDA, Alvaro
HIRATA, Mario H.
RODRIGUES, Alice C.
DOREA, Egidio L. FMUSP-HC
BERNIK, Marcia M. S.
BERTOLAMI, Marcelo C.
FALUDI, Andre A.
HIRATA, Rosario D. C.
dc.date.issued 2014
dc.identifier.citation JOURNAL OF CLINICAL LIPIDOLOGY, v.8, n.3, p.256-264, 2014
dc.identifier.issn 1933-2874
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/7975
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.publisher ELSEVIER SCIENCE INC
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
hcfmusp.author DOREA, Egidio L.:HU:DVCLME-62
hcfmusp.author.external · 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
hcfmusp.origem.id WOS:000335284200004
hcfmusp.origem.id 2-s2.0-84899711770
hcfmusp.publisher.city NEW YORK
hcfmusp.publisher.country USA
hcfmusp.relation.reference · Al-Waili Khalid, 2013, Oman Med J, V28, P48, DOI 10.5001/omj.2013.11
· [Anonymous], 2002, CIRCULATION, V106, P3143
· Aung LHH, 2011, LIPIDS HEALTH DIS, V10, DOI 10.1186/1476-511X-10-5
· Berge KE, 2006, ARTERIOSCL THROM VAS, V26, P1094, DOI 10.1161/01.ATV.0000204337.81286.1c
· Cerda A, 2010, CLIN CHIM ACTA, V411, P631, DOI 10.1016/j.cca.2010.01.002
· Cerda A, 2011, LIPIDS HEALTH DIS, V10, DOI 10.1186/1476-511X-10-206
· Chen SN, 2005, J AM COLL CARDIOL, V45, P1611, DOI 10.1016/j.jacc.2005.01.051
· Ding KY, 2008, PHARMACOGENET GENOM, V18, P169, DOI 10.1097/FPC.0b013e3282f44d99
· Evans D, 2006, BMC MED GENET, V7, DOI 10.1186/1471-2350-7-66
· Holla OL, 2011, J LIPID RES, V52, P1787, DOI 10.1194/jlr.M018093
· Huang CC, 2009, CIRC-CARDIOVASC GENE, V2, P354, DOI 10.1161/CIRCGENETICS.108.828467
· Kotowski IK, 2006, AM J HUM GENET, V78, P410, DOI 10.1086/500615
· Lopez D, 2008, BBA-MOL CELL BIOL L, V1781, P184, DOI 10.1016/j.bbalip.2008.01.003
· Mayne J, 2013, LIPIDS HEALTH DIS, V12, DOI 10.1186/1476-511X-12-70
· Mega JL, 2009, ARTERIOSCL THROM VAS, V29, P1310, DOI 10.1161/ATVBAHA.109.188474
· Minder CM, 2013, CURR OPIN CARDIOL, V28, P554, DOI 10.1097/HCO.0b013e32836429e6
· Naoumova RP, 2005, ARTERIOSCL THROM VAS, V25, P2654, DOI 10.1161/01.ATV.0000190668.94752.ab
· Pena SDJ, 2011, PLOS ONE, V6, DOI 10.1371/journal.pone.0017063
· Peters BJM, 2011, ATHEROSCLEROSIS, V217, P458, DOI 10.1016/j.atherosclerosis.2011.06.023
· Polisecki E, 2008, ATHEROSCLEROSIS, V200, P95, DOI 10.1016/j.atherosclerosis.2007.12.005
· Postmus I, 2012, PHARMACOGENOMICS, V13, P831, DOI [10.2217/pgs.12.25, 10.2217/PGS.12.25]
· Ramasamy I., 2013, CLIN CHEM LAB MED, V12, P1
· Rodrigues AC, 2011, INT J MOL SCI, V12, P5815, DOI 10.3390/ijms12095815
· Rodrigues AC, 2007, CURR OPIN MOL THER, V9, P545
· Rodrigues AC, 2013, CLIN CHIM ACTA, V417, P8, DOI 10.1016/j.cca.2012.11.028
· Salazar LA, 1998, CLIN CHEM, V44, P1748
· Scartezini M, 2007, CLIN SCI, V113, P435, DOI 10.1042/CS20070150
· Shioji K, 2004, J HUM GENET, V49, P109, DOI 10.1007/s10038-003-0114-3
· Silbiger VN, 2012, GENET TEST MOL BIOMA, V16, P524, DOI 10.1089/gtmb.2011.0267
· Soutar AK, 2007, NAT CLIN PRACT CARD, V4, P214, DOI 10.1038/ncpcardio0836
· Sposito AC, 2007, ARQ BRAS CARDIOL, V88, P2, DOI 10.1590/S0066-782X2007000700002
· Suarez-Kurtz Guilherme, 2012, Front Pharmacol, V3, P191, DOI 10.3389/fphar.2012.00191
· Sun H, 2012, ARTERIOSCL THROM VAS, V32, P1585, DOI 10.1161/ATVBAHA.112.250043
· Teslovich TM, 2010, NATURE, V466, P707, DOI 10.1038/nature09270
· Tveten K, 2012, HUM MOL GENET, V21, P1402, DOI 10.1093/hmg/ddr578
· Zhang DW, 2007, J BIOL CHEM, V282, P18602, DOI 10.1074/jbc.M702027200
· Zhou Q, 2009, CURR PHARM DESIGN, V15, P467
dc.description.index MEDLINE
dc.identifier.eissn 1876-4789
hcfmusp.citation.scopus 16
hcfmusp.citation.wos 15
hcfmusp.affiliation.country Brasil
hcfmusp.affiliation.country Chile


Files in this item

This item appears in the following Collection(s)

Show simple item record

Search DSpace



Browse

My Account

Statistics