000075786 001__ 75786
000075786 005__ 20200117212653.0
000075786 0247_ $$2doi$$a10.1371/journal.pone.0205430
000075786 0248_ $$2sideral$$a108780
000075786 037__ $$aART-2018-108780
000075786 041__ $$aeng
000075786 100__ $$aRuiz-Iruela, C.
000075786 245__ $$aKIF6 gene as a pharmacogenetic marker for lipid-lowering effect in statin treatment
000075786 260__ $$c2018
000075786 5060_ $$aAccess copy available to the general public$$fUnrestricted
000075786 5203_ $$aIntroduction The therapeutic response to statins has a high interindividual variability with respect to reductions in plasma LDL-cholesterol (c-LDL) and increases in HDL cholesterol (c-HDL). Many studies suggest that there is a relationship between the rs20455 KIF6 gene variant (c.2155T> C, Trp719Arg) and a lower risk of cardiovascular disease in patients being treated with statins. Aim The aim of this study was to investigate whether or not the c.2155T> C KIF6 gene variant modulates the hypercholesteremic effects of treatment with simvastatin, atorvastatin, or rosuvastatin. Materials and methods This was a prospective, observational and multicenter study. Three hundred and forty-four patients who had not undergone prior lipid-lowering treatment were recruited. Simvastatin, atorvastatin or rosuvastatin were administered. Lipid profiles and multiple clinical and biochemical variables were assessed before and after treatment. Results The c.2155T> C variant of the KIF6 gene was shown to influence physiological responses to treatment with simvastatin and atorvastatin. Patients who were homozygous for the c.2155T> C variant (CC genotype, ArgArg) had a 7.0% smaller reduction of LDL cholesterol levels (p = 0.015) in response to hypolipidemic treatment compared to patients with the TT (TrpTrp) or CT (TrpArg) genotype. After pharmacological treatment with rosuvastatin, patients carrying the genetic variant had an increase in c-HDL that was 21.9% lower compared to patients who did not carry the variant (p = 0.008). Conclusion Being a carrier of the c.2155T> C variant of the KIF6 gene negatively impacts patient responses to simvastatin, atorvastatin or rosuvastatin in terms of lipid lowering effect. Increasing the intensity of hypolipidemic therapy may be advisable for patients who are positive for the c.2155T> C variant.
000075786 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000075786 590__ $$a2.776$$b2018
000075786 591__ $$aMULTIDISCIPLINARY SCIENCES$$b23 / 69 = 0.333$$c2018$$dQ2$$eT2
000075786 592__ $$a1.1$$b2018
000075786 593__ $$aAgricultural and Biological Sciences (miscellaneous)$$c2018$$dQ1
000075786 593__ $$aMedicine (miscellaneous)$$c2018$$dQ1
000075786 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2018$$dQ1
000075786 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000075786 700__ $$aPadró-Miquel, A.
000075786 700__ $$aPintó-Sala, X.
000075786 700__ $$aBaena-Díez, N.
000075786 700__ $$aCaixàs-Pedragós, A.
000075786 700__ $$aGüell-Miró, R.
000075786 700__ $$aNavarro-Badal, R.
000075786 700__ $$aJusmet-Miguel, X.
000075786 700__ $$aCalmarza, P.
000075786 700__ $$0(orcid)0000-0002-1309-4363$$aPuzo-Foncilla, J.L.$$uUniversidad de Zaragoza
000075786 700__ $$aAlía-Ramos, P.
000075786 700__ $$aCandás-Estébanez, B.
000075786 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000075786 773__ $$g13, 10 (2018), e0205430[14 pp]$$pPLoS One$$tPloS one$$x1932-6203
000075786 8564_ $$s456046$$uhttps://zaguan.unizar.es/record/75786/files/texto_completo.pdf$$yVersión publicada
000075786 8564_ $$s95451$$uhttps://zaguan.unizar.es/record/75786/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000075786 909CO $$ooai:zaguan.unizar.es:75786$$particulos$$pdriver
000075786 951__ $$a2020-01-17-21:21:43
000075786 980__ $$aARTICLE