TY - JOUR
T1 - Common genetic variants do not associate with CAD in familial hypercholesterolemia
AU - van Iperen, Erik P. A.
AU - Sivapalaratnam, Suthesh
AU - Boekholdt, S. Matthijs
AU - Hovingh, G. Kees
AU - Maiwald, Stephanie
AU - Tanck, Michael W.
AU - Soranzo, Nicole
AU - Stephens, Jonathan C.
AU - Sambrook, Jennifer G.
AU - Levi, Marcel
AU - Ouwehand, Willem H.
AU - Kastelein, John Jp
AU - Trip, Mieke D.
AU - Zwinderman, Aeilko H.
PY - 2014
Y1 - 2014
N2 - In recent years, multiple loci dispersed on the genome have been shown to be associated with coronary artery disease (CAD). We investigated whether these common genetic variants also hold value for CAD prediction in a large cohort of patients with familial hypercholesterolemia (FH). We genotyped a total of 41 single-nucleotide polymorphisms (SNPs) in 1701 FH patients, of whom 482 patients (28.3%) had at least one coronary event during an average follow up of 66 years. The association of each SNP with event-free survival time was calculated with a Cox proportional hazard model. In the cardiovascular disease risk factor adjusted analysis, the most significant SNP was rs1122608:G>T in the SMARCA4 gene near the LDL-receptor (LDLR) gene, with a hazard ratio for CAD risk of 0.74 (95% CI 0.49-0.99; P-value 0.021). However, none of the SNPs reached the Bonferroni threshold. Of all the known CAD loci analyzed, the SMARCA4 locus near the LDLR had the strongest negative association with CAD in this high-risk FH cohort. The effect is contrary to what was expected. None of the other loci showed association with CAD
AB - In recent years, multiple loci dispersed on the genome have been shown to be associated with coronary artery disease (CAD). We investigated whether these common genetic variants also hold value for CAD prediction in a large cohort of patients with familial hypercholesterolemia (FH). We genotyped a total of 41 single-nucleotide polymorphisms (SNPs) in 1701 FH patients, of whom 482 patients (28.3%) had at least one coronary event during an average follow up of 66 years. The association of each SNP with event-free survival time was calculated with a Cox proportional hazard model. In the cardiovascular disease risk factor adjusted analysis, the most significant SNP was rs1122608:G>T in the SMARCA4 gene near the LDL-receptor (LDLR) gene, with a hazard ratio for CAD risk of 0.74 (95% CI 0.49-0.99; P-value 0.021). However, none of the SNPs reached the Bonferroni threshold. Of all the known CAD loci analyzed, the SMARCA4 locus near the LDLR had the strongest negative association with CAD in this high-risk FH cohort. The effect is contrary to what was expected. None of the other loci showed association with CAD
U2 - https://doi.org/10.1038/ejhg.2013.242
DO - https://doi.org/10.1038/ejhg.2013.242
M3 - Article
C2 - 24219970
SN - 1018-4813
VL - 22
SP - 809
EP - 813
JO - European journal of human genetics
JF - European journal of human genetics
IS - 6
ER -