Abstract
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.
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Acknowledgements
This work was supported by Bloodomics consortium, European Union 6th Framework Programme (LSHM-CT-2004-503485), Ipse Movet, the Lifetime Achievement Award of the Dutch Heart Foundation (2010T082) to JJPK and grants from the British Heart Foundation and the National Institute for Health Research, England to WHO. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
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van Iperen, E., Sivapalaratnam, S., Boekholdt, S. et al. Common genetic variants do not associate with CAD in familial hypercholesterolemia. Eur J Hum Genet 22, 809–813 (2014). https://doi.org/10.1038/ejhg.2013.242
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DOI: https://doi.org/10.1038/ejhg.2013.242
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