OBJECTIVES: Recently, a significant impact of a new locus on chromosome 1p13.3 on serum LDL (low-density lipoprotein) cholesterol and clinical events of coronary artery disease (CAD) was described. Potential associations between variants on this locus and angiographically characterized coronary atherosclerosis are unknown. We therefore aimed at investigating the association of variants of locus 1p13.3 with coronary atherosclerosis. METHODS: We performed genotyping of variants rs599839, rs646776, and rs4970834 on chromosome 1p13.3 in a large cohort of 1610 consecutive Caucasian patients undergoing coronary angiography, where lesions of 50% or more were classified as significant. RESULTS: Compared to the homozygous common allele the rare alleles of variants rs599839, rs646776, and rs4970834 were significantly associated with decreased serum LDL cholesterol (132+/-40mg/dl vs. 125+/-36mg/dl, P=0.003, 132+/-40mg/dl vs. 124+/-36mg/dl, P<0.001, and 131+/-40mg/dl vs. 125+/-37mg/dl, P=0.005, respectively). Further, carriers of the rare alleles of variants rs599839 and rs646776 were at a significantly lower risk of significant coronary stenoses than subjects who were homozygous for the frequent alleles, with odds ratios (ORs) of 0.78 [0.63-0.96]; P=0.019 and 0.74 [0.60-0.91]; P=0.004, respectively. After multivariate adjustment including LDL cholesterol, the protective effect of the rare allele of variant rs646776, but not of variant rs599839, on CAD risk remained significant (OR=0.77 [0.61-0.98], P=0.034). CONCLUSIONS: We conclude that chromosomal locus 1p13.3 is significantly associated with both, serum LDL cholesterol and coronary atherosclerotic lesions.
OBJECTIVES: Recently, a significant impact of a new locus on chromosome 1p13.3 on serum LDL (low-density lipoprotein) cholesterol and clinical events of coronary artery disease (CAD) was described. Potential associations between variants on this locus and angiographically characterized coronary atherosclerosis are unknown. We therefore aimed at investigating the association of variants of locus 1p13.3 with coronary atherosclerosis. METHODS: We performed genotyping of variants rs599839, rs646776, and rs4970834 on chromosome 1p13.3 in a large cohort of 1610 consecutive Caucasian patients undergoing coronary angiography, where lesions of 50% or more were classified as significant. RESULTS: Compared to the homozygous common allele the rare alleles of variants rs599839, rs646776, and rs4970834 were significantly associated with decreased serum LDL cholesterol (132+/-40mg/dl vs. 125+/-36mg/dl, P=0.003, 132+/-40mg/dl vs. 124+/-36mg/dl, P<0.001, and 131+/-40mg/dl vs. 125+/-37mg/dl, P=0.005, respectively). Further, carriers of the rare alleles of variants rs599839 and rs646776 were at a significantly lower risk of significant coronary stenoses than subjects who were homozygous for the frequent alleles, with odds ratios (ORs) of 0.78 [0.63-0.96]; P=0.019 and 0.74 [0.60-0.91]; P=0.004, respectively. After multivariate adjustment including LDL cholesterol, the protective effect of the rare allele of variant rs646776, but not of variant rs599839, on CAD risk remained significant (OR=0.77 [0.61-0.98], P=0.034). CONCLUSIONS: We conclude that chromosomal locus 1p13.3 is significantly associated with both, serum LDL cholesterol and coronary atherosclerotic lesions.
Authors: Harald Grallert; Josée Dupuis; Joshua C Bis; Abbas Dehghan; Maja Barbalic; Jens Baumert; Chen Lu; Nicholas L Smith; André G Uitterlinden; Robert Roberts; Natalie Khuseyinova; Renate B Schnabel; Kenneth M Rice; Fernando Rivadeneira; Ron C Hoogeveen; João Daniel Fontes; Christa Meisinger; John F Keaney; Rozenn Lemaitre; Yurii S Aulchenko; Ramachandran S Vasan; Stephen Ellis; Stanley L Hazen; Cornelia M van Duijn; Jeanenne J Nelson; Winfried März; Heribert Schunkert; Ruth M McPherson; Heide A Stirnadel-Farrant; Bruce M Psaty; Christian Gieger; David Siscovick; Albert Hofman; Thomas Illig; Mary Cushman; Jennifer F Yamamoto; Jerome I Rotter; Martin G Larson; Alexandre F R Stewart; Eric Boerwinkle; Jacqueline C M Witteman; Russell P Tracy; Wolfgang Koenig; Emelia J Benjamin; Christie M Ballantyne Journal: Eur Heart J Date: 2011-10-14 Impact factor: 29.983
Authors: Minerva M Carrasquillo; Alexandra M Nicholson; NiCole Finch; J Raphael Gibbs; Matt Baker; Nicola J Rutherford; Talisha A Hunter; Mariely DeJesus-Hernandez; Gina D Bisceglio; Ian R Mackenzie; Andrew Singleton; Mark R Cookson; Julia E Crook; Allissa Dillman; Dena Hernandez; Ronald C Petersen; Neill R Graff-Radford; Steven G Younkin; Rosa Rademakers Journal: Am J Hum Genet Date: 2010-11-18 Impact factor: 11.025
Authors: James Ronald; Ramakrishnan Rajagopalan; Jane E Ranchalis; Julieann K Marshall; Thomas S Hatsukami; Patrick J Heagerty; Gail P Jarvik Journal: Lipids Health Dis Date: 2009-12-01 Impact factor: 3.876