Department of Clinical Chemistry, University of Tampere, Medical School, and Tampere University Hospital, Tampere, Finland.
PLoS One. 2012;7(1):e28931. doi: 10.1371/journal.pone.0028931. Epub 2012 Jan 25.
Genome-wide association studies (GWASs) have identified a large number of variants (SNPs) associating with an increased risk of coronary artery disease (CAD). Recently, the CARDIoGRAM consortium published a GWAS based on the largest study population so far. They successfully replicated twelve already known associations and discovered thirteen new SNPs associating with CAD. We examined whether the genetic profiling of these variants improves prediction of subclinical atherosclerosis--i.e., carotid intima-media thickness (CIMT) and carotid artery elasticity (CAE)--beyond classical risk factors.
We genotyped 24 variants found in a population of European ancestry and measured CIMT and CAE in 2001 and 2007 from 2,081, and 2,015 subjects (aged 30-45 years in 2007) respectively, participating in the Cardiovascular Risk in Young Finns Study (YFS). The Bogalusa Heart Study (BHS; n = 1179) was used as a replication cohort (mean age of 37.5). For additional replication, a sub-sample of 5 SNPs was genotyped for 1,291 individuals aged 46-76 years participating in the Health 2000 population survey. We tested the impact of genetic risk score (GRS(24SNP/CAD)) calculated as a weighted (by allelic odds ratios for CAD) sum of CAD risk alleles from the studied 24 variants on CIMT, CAE, the incidence of carotid atherosclerosis and the progression of CIMT and CAE during a 6-year follow-up.
CIMT or CAE did not significantly associate with GRS(24SNP/CAD) before or after adjusting for classical CAD risk factors (p>0.05 for all) in YFS or in the BHS. CIMT and CAE associated with only one SNP each in the YFS. The findings were not replicated in the replication cohorts. In the meta-analysis CIMT or CAE did not associate with any of the SNPs.
Genetic profiling, by using known CAD risk variants, should not improve risk stratification for subclinical atherosclerosis beyond conventional risk factors among healthy young adults.
全基因组关联研究（GWAS）已经确定了许多与冠心病（CAD）风险增加相关的变异（SNP）。最近，CARDIOGRAM 联盟发表了一项迄今为止基于最大研究人群的 GWAS。他们成功复制了 12 个已知的关联，并发现了 13 个与 CAD 相关的新 SNP。我们研究了这些变体的遗传特征是否可以改善对亚临床动脉粥样硬化（即颈动脉内膜中层厚度（CIMT）和颈动脉弹性（CAE））的预测，而不仅仅是基于传统的危险因素。
我们对欧洲血统人群中的 24 个变体进行了基因分型，并分别在 2001 年和 2007 年测量了 2081 名和 2015 名（2007 年年龄为 30-45 岁）受试者的 CIMT 和 CAE，他们参加了心血管风险在年轻的芬兰人研究（YFS）。Bogalusa 心脏研究（BHS；n=1179）被用作复制队列（平均年龄为 37.5 岁）。为了进一步验证，对 5 个 SNP 的亚样本进行了基因分型，样本量为 1291 名年龄在 46-76 岁之间的个体，他们参加了健康 2000 人群调查。我们测试了遗传风险评分（GRS（24SNP/CAD））的影响，该评分是通过对研究的 24 个变体中的 CAD 风险等位基因进行加权（加权比为 CAD 的等位基因比值）而计算得出的，用于 CIMT、CAE、颈动脉粥样硬化的发生率以及 6 年随访期间 CIMT 和 CAE 的进展情况。
在 YFS 或 BHS 中，CIMT 或 CAE 与 GRS（24SNP/CAD）在调整了传统 CAD 危险因素之前或之后均无显著相关性（所有 P>0.05）。YFS 中 CIMT 和 CAE 仅与一个 SNP 相关。在复制队列中未发现这些结果。在荟萃分析中，CIMT 或 CAE 与任何 SNP 均无关联。
在健康的年轻成年人中，使用已知的 CAD 风险变异进行遗传特征分析，不应改善对亚临床动脉粥样硬化的风险分层，而不仅仅是基于传统的危险因素。
