Lee Ji-Young, Kim Gwangsil, Park Sungha, Kang Seok-Min, Jang Yangsoo, Lee Sang-Hak
Cardiovascular Research Institute and Cardiovascular Genome Center, Yonsei University Health System.
J Atheroscler Thromb. 2015;22(4):363-71. doi: 10.5551/jat.26047. Epub 2014 Oct 17.
In this study, we investigated the genetic determinants of lesion characteristics and the severity of coronary artery disease (CAD) using a genome-wide association study (GWAS) and replication genotyping.
The discovery set for GWAS consisted of 667 patients exhibiting angiographically diagnosed CAD with symptoms. For replication genotyping, 837 age- and sex-matched CAD patients were selected. Genetic determinants of lesion characteristics (diffuse vs. non-diffuse lesions), the number of diseased vessels (multi-vessel vs. single vessel disease) and the modified Duke score (high vs. low), which indicates the severity of CAD, were analyzed after adjusting for confounding factors.
Single nucleotide polymorphisms (SNPs) rs12917449, rs10152898 and rs231150 were associated with diffuse lesions, while rs1225006 and rs6745588 were associated with multi-vessel disease. However, on replication genotyping, no significant associations were found between any of these five SNPs and the lesion characteristics or CAD severity. In contrast, in the combined population of both the discovery and replication sets, genotypes rs125006 of CPNE4 and rs231150 of TRPS1 were found to be significantly associated with the modified Duke score. The addition of rs1225006 to conventional risk factors had significant incremental value in the model of the score.
The associations between five SNPs identified using GWAS and angiographic characteristics were not significant in the current replication study. However, two variants, particularly rs1225006, were found to be associated with the severity of CAD in the combined set. These results indicate the potential clinical implication of these variants with respect to the risk of CAD.
在本研究中，我们使用全基因组关联研究（GWAS）和重复基因分型来研究病变特征和冠状动脉疾病（CAD）严重程度的遗传决定因素。
GWAS的发现集由667例经血管造影诊断为有症状CAD的患者组成。为进行重复基因分型，选择了837例年龄和性别匹配的CAD患者。在调整混杂因素后，分析病变特征（弥漫性病变与非弥漫性病变）、病变血管数量（多支血管病变与单支血管病变）以及表明CAD严重程度的改良杜克评分（高评分与低评分）的遗传决定因素。
单核苷酸多态性（SNP）rs12917449、rs10152898和rs231150与弥漫性病变相关，而rs1225006和rs6745588与多支血管病变相关。然而，在重复基因分型中，这五个SNP中的任何一个与病变特征或CAD严重程度之间均未发现显著关联。相比之下，在发现集和重复集的合并人群中，发现CPNE4的rs125006基因型和TRPS1的rs231150基因型与改良杜克评分显著相关。在评分模型中，将rs1225006添加到传统危险因素中具有显著的增量价值。
在当前的重复研究中，使用GWAS鉴定的五个SNP与血管造影特征之间的关联不显著。然而，在合并集中发现两个变异，特别是rs1225006，与CAD的严重程度相关。这些结果表明这些变异在CAD风险方面的潜在临床意义。
