Common genetic variants do not associate with CAD in familial hypercholesterolemia.

Autor: van Iperen EP; 1] Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam, The Netherlands [2] Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands., Sivapalaratnam S; Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands., Boekholdt SM; 1] Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands [2] Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands., Hovingh GK; Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands., Maiwald S; Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands., Tanck MW; Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam, The Netherlands., Soranzo N; Human Genetics, Welcome Trust Sanger Institute, Hinxton, UK., Stephens JC; 1] Department of Haematology, University of Cambridge, Cambridge, UK [2] National Health Service Blood and Transplant, Cambridge, UK., Sambrook JG; 1] Department of Haematology, University of Cambridge, Cambridge, UK [2] National Health Service Blood and Transplant, Cambridge, UK., Levi M; Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands., Ouwehand WH; 1] Human Genetics, Welcome Trust Sanger Institute, Hinxton, UK [2] Department of Haematology, University of Cambridge, Cambridge, UK [3] National Health Service Blood and Transplant, Cambridge, UK., Kastelein JJ; Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands., Trip MD; Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands., Zwinderman AH; Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: European journal of human genetics : EJHG [Eur J Hum Genet] 2014 Jun; Vol. 22 (6), pp. 809-13. Date of Electronic Publication: 2013 Nov 13.
DOI: 10.1038/ejhg.2013.242
Abstrakt: 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.
Databáze: MEDLINE
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