A common KIF6 polymorphism increases vulnerability to low-density lipoprotein cholesterol: two meta-analyses and a meta-regression analysis.

<h4>Background</h4>We sought to determine if a common polymorphism can influence vulnerability to LDL cholesterol, and thereby influence the clinical benefit derived from therapies that reduce LDL cholesterol.<h4>Methods</h4>We conducted a meta-analysis of the association bet...

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Autores principales:	Brian A Ference, Wonsuk Yoo, John M Flack, Michael Clarke
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/350a104c561d4a4ab589b1161eaf662a
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spelling	oai:doaj.org-article:350a104c561d4a4ab589b1161eaf662a2021-11-18T07:31:44ZA common KIF6 polymorphism increases vulnerability to low-density lipoprotein cholesterol: two meta-analyses and a meta-regression analysis.1932-620310.1371/journal.pone.0028834https://doaj.org/article/350a104c561d4a4ab589b1161eaf662a2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22216121/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>We sought to determine if a common polymorphism can influence vulnerability to LDL cholesterol, and thereby influence the clinical benefit derived from therapies that reduce LDL cholesterol.<h4>Methods</h4>We conducted a meta-analysis of the association between a common Trp719Arg polymorphism in the kinesin-like protein 6 (KIF6) gene and the risk of cardiovascular disease (CVD), and a meta-regression analysis to measure the effect modification of this polymorphism on the association between LDL cholesterol and the risk of CVD. We used this measure of genetic effect modification to predict the expected difference in clinical benefit among KIF6 719Arg allele carriers and non-carriers in response to therapies that reduce LDL cholesterol. We then conducted a meta-analysis of statin trials to compare the expected difference in clinical benefit with the observed difference during treatment with a statin.<h4>Results</h4>In a meta-analysis involving 144,931 participants, the KIF6 719Arg allele was not associated with the relative risk (RR) of CVD (RR: 1.02, 95%CI: 0.98-1.07, p=0.288). Meta-regression analysis involving 88,535 participants, however, showed that the 719Arg allele appears to influence the effect of LDL cholesterol on the risk of CVD. KIF6 carriers experienced a 13% greater reduction in the risk of CVD per mmol/L decrease in LDL cholesterol than non-carriers. We interpreted this difference as the expected difference in clinical benefit among KIF6 carriers and non-carriers in response to therapies that lower LDL cholesterol. The difference in clinical benefit predicted by the increased vulnerability to LDL cholesterol among KIF6 carriers (ratio of RR: 0.87, 95%CI: 0.80-0.94, p = 0.001) agreed very closely with the observed difference among 50,060 KIF6 carriers and non-carriers enrolled in 8 randomized trials of statin therapy (ratio of RR: 0.87, 95%CI: 0.77-0.99, p=0.038).<h4>Conclusion</h4>The KIF6 719Arg allele increases vulnerability to LDL cholesterol and thereby influences the expected clinical benefit of therapies that reduce LDL cholesterol.Brian A FerenceWonsuk YooJohn M FlackMichael ClarkePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e28834 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Brian A Ference Wonsuk Yoo John M Flack Michael Clarke A common KIF6 polymorphism increases vulnerability to low-density lipoprotein cholesterol: two meta-analyses and a meta-regression analysis.
description	<h4>Background</h4>We sought to determine if a common polymorphism can influence vulnerability to LDL cholesterol, and thereby influence the clinical benefit derived from therapies that reduce LDL cholesterol.<h4>Methods</h4>We conducted a meta-analysis of the association between a common Trp719Arg polymorphism in the kinesin-like protein 6 (KIF6) gene and the risk of cardiovascular disease (CVD), and a meta-regression analysis to measure the effect modification of this polymorphism on the association between LDL cholesterol and the risk of CVD. We used this measure of genetic effect modification to predict the expected difference in clinical benefit among KIF6 719Arg allele carriers and non-carriers in response to therapies that reduce LDL cholesterol. We then conducted a meta-analysis of statin trials to compare the expected difference in clinical benefit with the observed difference during treatment with a statin.<h4>Results</h4>In a meta-analysis involving 144,931 participants, the KIF6 719Arg allele was not associated with the relative risk (RR) of CVD (RR: 1.02, 95%CI: 0.98-1.07, p=0.288). Meta-regression analysis involving 88,535 participants, however, showed that the 719Arg allele appears to influence the effect of LDL cholesterol on the risk of CVD. KIF6 carriers experienced a 13% greater reduction in the risk of CVD per mmol/L decrease in LDL cholesterol than non-carriers. We interpreted this difference as the expected difference in clinical benefit among KIF6 carriers and non-carriers in response to therapies that lower LDL cholesterol. The difference in clinical benefit predicted by the increased vulnerability to LDL cholesterol among KIF6 carriers (ratio of RR: 0.87, 95%CI: 0.80-0.94, p = 0.001) agreed very closely with the observed difference among 50,060 KIF6 carriers and non-carriers enrolled in 8 randomized trials of statin therapy (ratio of RR: 0.87, 95%CI: 0.77-0.99, p=0.038).<h4>Conclusion</h4>The KIF6 719Arg allele increases vulnerability to LDL cholesterol and thereby influences the expected clinical benefit of therapies that reduce LDL cholesterol.
format	article
author	Brian A Ference Wonsuk Yoo John M Flack Michael Clarke
author_facet	Brian A Ference Wonsuk Yoo John M Flack Michael Clarke
author_sort	Brian A Ference
title	A common KIF6 polymorphism increases vulnerability to low-density lipoprotein cholesterol: two meta-analyses and a meta-regression analysis.
title_short	A common KIF6 polymorphism increases vulnerability to low-density lipoprotein cholesterol: two meta-analyses and a meta-regression analysis.
title_full	A common KIF6 polymorphism increases vulnerability to low-density lipoprotein cholesterol: two meta-analyses and a meta-regression analysis.
title_fullStr	A common KIF6 polymorphism increases vulnerability to low-density lipoprotein cholesterol: two meta-analyses and a meta-regression analysis.
title_full_unstemmed	A common KIF6 polymorphism increases vulnerability to low-density lipoprotein cholesterol: two meta-analyses and a meta-regression analysis.
title_sort	common kif6 polymorphism increases vulnerability to low-density lipoprotein cholesterol: two meta-analyses and a meta-regression analysis.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/350a104c561d4a4ab589b1161eaf662a
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A common KIF6 polymorphism increases vulnerability to low-density lipoprotein cholesterol: two meta-analyses and a meta-regression analysis.

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