Vaara Satu, Tikkanen Emmi, Parkkonen Olavi, Lokki Marja-Liisa, Ripatti Samuli, Perola Markus, Nieminen Markku S, Sinisalo Juha
From the Division of Cardiology, Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland (S.V., O.P., M.S.N., J.S.); Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (E.T., S.P., M.P.); and Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland (E.T., S.P., M.P.) and Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland (M.-L.L.).
Circ Cardiovasc Genet. 2016 Apr;9(2):172-8. doi: 10.1161/CIRCGENETICS.115.001271. Epub 2016 Mar 15.
Several clinical risk estimation tools have established their role in the prediction of recurrence of acute coronary syndrome (ACS), but the value of genetic risk scores (GRSs) remains unclear. We examined how well 2 different GRSs estimate recurrent ACS and whether clinical factors are associated with GRSs.
A cohort of 2090 consecutive patients with ACS who underwent coronary angiography between July 2006 and March 2008 in a single tertiary center was genotyped and prospectively followed up for a median of 5.5 years. We formed 2 partially overlapping GRSs: GRS47 of 47 single-nucleotide polymorphisms with previously reported significant association with coronary artery disease and GRS153 of 153 single-nucleotide polymorphisms with significant or suggestive association with coronary artery disease. GRS47 showed association with recurrent ACS independent of clinical factors (P=0.037; hazard ratio, 1.17; 95% confidence interval, 1.01-1.36). GRS153 had no association with either recurrent ACS or composite of recurrent ACS or death. Also, GRS47 was associated inversely with smoking and ST-segment-elevation myocardial infarction (P=0.004; odds ratio, 0.22; 95% confidence interval, 0.08-0.62 and P=0.041; odds ratio, 0.36; 95% confidence interval, 0.13-0.96, respectively).
GRSs combined of 47 known coronary artery disease risk single-nucleotide polymorphisms were associated with recurrent ACS after multivariable adjustments in a heterogenic ACS population for the first time. Smoking and ST-segment-elevation myocardial infarction had an inverse association with the GRSs. The significance of smoking in relation to genetic coronary artery disease predisposition may merit further evaluation in patients with ACS.
几种临床风险评估工具已在急性冠状动脉综合征（ACS）复发预测中确立了其作用，但基因风险评分（GRS）的价值仍不明确。我们研究了两种不同的GRS对复发性ACS的估计效果以及临床因素是否与GRS相关。
2006年7月至2008年3月在一个单一的三级中心连续接受冠状动脉造影的2090例ACS患者队列进行了基因分型，并进行了中位时间为5.5年的前瞻性随访。我们构建了两个部分重叠的GRS：包含47个单核苷酸多态性的GRS47，这些单核苷酸多态性先前已报道与冠状动脉疾病有显著关联；以及包含153个单核苷酸多态性的GRS153，这些单核苷酸多态性与冠状动脉疾病有显著或提示性关联。GRS47显示与复发性ACS相关，且独立于临床因素（P = 0.037；风险比，1.17；95%置信区间，1.01 - 1.36）。GRS153与复发性ACS或复发性ACS与死亡的复合终点均无关联。此外，GRS47与吸烟和ST段抬高型心肌梗死呈负相关（分别为P = 0.004；比值比，0.22；95%置信区间，0.08 - 0.62和P = 0.041；比值比，0.36；95%置信区间，0.13 - 0.96）。
首次在异质性ACS人群中进行多变量调整后，由47个已知的冠状动脉疾病风险单核苷酸多态性组成的GRS与复发性ACS相关。吸烟和ST段抬高型心肌梗死与GRS呈负相关。吸烟与遗传性冠状动脉疾病易感性的关系在ACS患者中可能值得进一步评估。
