颈动脉粥样硬化基因座对心血管事件的影响。
Impact of carotid atherosclerosis loci on cardiovascular events.
作者信息
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
机构信息
Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands; CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil.
Laboratory of Experimental Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
出版信息
Atherosclerosis. 2015 Dec;243(2):466-8. doi: 10.1016/j.atherosclerosis.2015.10.017. Epub 2015 Oct 19.
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.
背景
全基因组关联研究（GWAS）已鉴定出六个与颈动脉内膜中层厚度（cIMT）或斑块相关的单核苷酸多态性（SNP）。然而，这些基因座是否与其他血管疾病及随后的血管事件相关尚不清楚。
方法与结果
我们在动脉疾病的二次表现（SMART）队列中，检测了六个SNP（rs4888378、rs11781551、rs445925、rs6601530、rs17398575和rs1878406）与亚临床动脉粥样硬化指标（cIMT、斑块存在情况和踝臂指数）以及缺血性中风、腹主动脉瘤、外周或冠状动脉疾病（CAD）之间的关联。四个SNP与cIMT相关，两个与斑块相关（p < 0.05）。一个SNP也与CAD显著相关（rs1878406，OR = 1.24，95% CI = 1.08 - 1.42，p = 2×10⁻³）。基于与cIMT相关的SNP构建的遗传风险评分（GRS）与cIMT本身风险增加相关（p = 1×10⁻³），但与随访期间的其他次要结局或血管事件无关（p = 0.86）。
结论
除了重复先前发表的cIMT关联外，我们证实了GRS与cIMT之间存在名义上的显著效应。
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