caa a22 4500 445861304 CHVBK 20180317145444.0 cr unu---uuuuu 170323e20110101xx s 000 0 eng 10.1007/s00439-010-0892-6 doi (NATIONALLICENCE)springer-10.1007/s00439-010-0892-6 Genetic variants in the KIF6 region and coronary event reduction from statin therapy [Elektronische Daten] [Yonghong Li, Marc Sabatine, Carmen Tong, Ian Ford, Todd Kirchgessner, Christopher Packard, Michele Robertson, Charles Rowland, Lance Bare, James Shepherd, James Devlin, Olga Iakoubova] A single nucleotide polymorphism (SNP) in KIF6, a member of the KIF9 family of kinesins, is associated with differential coronary event reduction from statin therapy in four randomized controlled trials; this SNP (rs20455) is also associated with the risk for coronary heart disease (CHD) in multiple prospective studies. We investigated whether other common SNPs in the KIF6 region were associated with event reduction from statin therapy. Of the 170 SNPs in the KIF6 region investigated in the Cholesterol and Recurrent Events trial (CARE), 28 were associated with differential event reduction from statin therapy (P interaction<0.1 in Caucasians, adjusted for age and sex) and were further investigated in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI22) and West of Scotland Coronary Prevention Study (WOSCOPS). These analyses revealed that two SNPs (rs9462535 and rs9471077), in addition to rs20455, were associated with event reduction from statin therapy (P interaction<0.1 in each of the three studies). The relative risk reduction ranged from 37 to 50% (P<0.01) in carriers of the minor alleles of these SNPs and from −4 to 13% (P>0.4) in non-carriers. These three SNPs are in high linkage disequilibrium with one another (r 2>0.84). Functional studies of these variants may help to understand the role of KIF6 in the pathogenesis of CHD and differential response to statin therapy. The Author(s), 2010 Li Yonghong Celera, 94502, Alameda, CA, USA aut Sabatine Marc Brigham & Women's Hospital, Harvard Medical School, 02115, Boston, MA, USA aut Tong Carmen Celera, 94502, Alameda, CA, USA aut Ford Ian University of Glasgow and Royal Infirmary, Glasgow, Scotland, UK aut Kirchgessner Todd Pharmaceutical Research Institute, Bristol-Myers Squibb, 08543, Princeton, NJ, USA aut Packard Christopher University of Glasgow and Royal Infirmary, Glasgow, Scotland, UK aut Robertson Michele University of Glasgow and Royal Infirmary, Glasgow, Scotland, UK aut Rowland Charles Celera, 94502, Alameda, CA, USA aut Bare Lance Celera, 94502, Alameda, CA, USA aut Shepherd James University of Glasgow and Royal Infirmary, Glasgow, Scotland, UK aut Devlin James Celera, 94502, Alameda, CA, USA aut Iakoubova Olga Celera, 94502, Alameda, CA, USA aut Human Genetics Springer-Verlag 129/1(2011-01-01), 17-23 0340-6717 129:1<17 2011 129 439 https://doi.org/10.1007/s00439-010-0892-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-010-0892-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li Yonghong Celera, 94502, Alameda, CA, USA aut NATIONALLICENCE 700 1- Sabatine Marc Brigham & Women's Hospital, Harvard Medical School, 02115, Boston, MA, USA aut NATIONALLICENCE 700 1- Tong Carmen Celera, 94502, Alameda, CA, USA aut NATIONALLICENCE 700 1- Ford Ian University of Glasgow and Royal Infirmary, Glasgow, Scotland, UK aut NATIONALLICENCE 700 1- Kirchgessner Todd Pharmaceutical Research Institute, Bristol-Myers Squibb, 08543, Princeton, NJ, USA aut NATIONALLICENCE 700 1- Packard Christopher University of Glasgow and Royal Infirmary, Glasgow, Scotland, UK aut NATIONALLICENCE 700 1- Robertson Michele University of Glasgow and Royal Infirmary, Glasgow, Scotland, UK aut NATIONALLICENCE 700 1- Rowland Charles Celera, 94502, Alameda, CA, USA aut NATIONALLICENCE 700 1- Bare Lance Celera, 94502, Alameda, CA, USA aut NATIONALLICENCE 700 1- Shepherd James University of Glasgow and Royal Infirmary, Glasgow, Scotland, UK aut NATIONALLICENCE 700 1- Devlin James Celera, 94502, Alameda, CA, USA aut NATIONALLICENCE 700 1- Iakoubova Olga Celera, 94502, Alameda, CA, USA aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 129/1(2011-01-01), 17-23 0340-6717 129:1<17 2011 129 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer