Impact of carotid atherosclerosis loci on cardiovascular events. Issue 2 (December 2015)

• Record Type: Journal Article
• Authors: Hemerich, Daiane; van der Laan, Sander W.; Tragante, Vinicius; den Ruijter, Hester M.; de Borst, Gert Jan; Pasterkamp, Gerard; de Bakker, Paul I.W.; Asselbergs, Folkert W.
• Is Part Of: Atherosclerosis. Volume 243:Issue 2(2015)
• Page Start: 466
• Page End: 468
• Publication Date: 2015-12
• Subjects: Atherosclerosis -- Single-nucleotide polymorphisms -- Carotid intima-media thickness -- Plaque; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.10.017
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background: Genome-wide association studies (GWAS) have identified six single-nucleotide polymorphisms (SNPs) related to carotid intima media thickness (cIMT) or plaque. However, whether these loci relate to other vascular diseases and subsequent vascular events is unclear. Methods and results: We tested six SNPs (rs4888378, rs11781551, rs445925, rs6601530, rs17398575 and rs1878406) for association with subclinical atherosclerotic measures (cIMT, plaque presence and ankle-brachial index), as well as ischemic stroke, abdominal aortic aneurysm, peripheral or coronary artery disease (CAD) in the Second Manifestations of ARTerial disease (SMART) cohort. Four SNPs were associated with cIMT and two with plaque (p < 0.05). One SNP was also significantly associated to CAD (rs1878406, OR = 1.24, 95% CI = 1.08–1.42, p = 2 × 10 −3 ). A genetic risk score (GRS) based on the cIMT-related SNPs was associated to increased risk of cIMT itself (p = 1 × 10 −3 ), but not to other secondary outcomes or vascular events during follow-up (p = 0.86). Conclusions: In addition to replicating previously published associations for cIMT, we confirmed a nominally significant effect between the GRS and cIMT. Highlights: We tested 6 variants related to carotid atherosclerosis for replication and association to other vascular beds in SMART. We replicated the association of 4 SNPs (p < 0.05), with a direction of effect similar to previous reports (binomial p = 0.03). One SNP was associated with CAD (odds ratio = 1.24, 95% C.I. 1.08–1.42, p = 2 × 10 −3 ), adding evidence to previous reports. A genetic risk score based on cIMT-related SNPs was associated with cIMT (p = 1 × 10 −3 ). The genetic risk score was not associated to clinical events during follow-up (p = 0.86).