多支冠状动脉疾病患者中与染色体 9p21 多态性相关的死亡率更高。
Higher incidence of death in multi-vessel coronary artery disease patients associated with polymorphisms in chromosome 9p21.
机构信息
Laboratory of Genetics and Molecular Cardiology, Heart Institute, Sao Paulo University Medical School, Av, Dr, Enéas de Carvalho Aguiar, 44 Cerqueira César, Sao Paulo, SP, Brazil.
出版信息
BMC Cardiovasc Disord. 2012 Aug 2;12:61. doi: 10.1186/1471-2261-12-61.
BACKGROUND
We investigated whether 9p21 polymorphisms are associated with cardiovascular events in a group of 611 patients enrolled in the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease (CAD) and preserved left ventricular function.
METHODS
The participants of the MASS II were genotyped for 9p21 polymorphisms (rs10757274, rs2383206, rs10757278 and rs1333049). Survival curves were calculated with the Kaplan-Meier method and compared with the log-rank statistic. We assessed the relationship between baseline variables and the composite end-point of death, death from cardiac causes and myocardial infarction using a Cox proportional hazards survival model.
RESULTS
We observed significant differences between patients within each polymorphism genotype group for baseline characteristics. The frequency of diabetes was lower in patients carrying GG genotype for rs10757274, rs2383206 and rs10757278 (29.4%, 32.8%, 32.0%) compared to patients carrying AA or AG genotypes (49.1% and 39.2%, p = 0.01; 52.4% and 40.1%, p = 0.01; 47.8% and 37.9%, p = 0.04; respectively). Significant differences in genotype frequencies between double and triple vessel disease patients were observed for the rs10757274, rs10757278 and rs1333049. Finally, there was a higher incidence of overall mortality in patients with the GG genotype for rs2383206 compared to patients with AA and AG genotypes (19.5%, 11.9%, 11.0%, respectively; p = 0.04). Moreover, the rs2383206 was still significantly associated with a 1.75-fold increased risk of overall mortality (p = 0.02) even after adjustment of a Cox multivariate model for age, previous myocardial infarction, diabetes, smoking and type of coronary anatomy.
CONCLUSIONS
Our data are in accordance to previous evidence that chromosome 9p21 genetic variation may constitute a genetic modulator in the cardiovascular system in different scenarios. In patients with established CAD, we observed an association between the rs2383206 and higher incidence of overall mortality and death from cardiac causes in patients with multi-vessel CAD.
背景
我们调查了 611 名参加医学、血管成形术或手术研究 II（MASS II）的患者中 9p21 多态性是否与心血管事件相关，这是一项比较冠心病（CAD）和保留左心室功能患者治疗的随机试验。
方法
MASS II 的参与者针对 9p21 多态性（rs10757274、rs2383206、rs10757278 和 rs1333049）进行基因分型。使用 Kaplan-Meier 方法计算生存曲线，并与对数秩统计进行比较。我们使用 Cox 比例风险生存模型评估基线变量与死亡、心脏原因死亡和心肌梗死复合终点之间的关系。
结果
我们观察到每个多态性基因型组内的患者之间存在显著的基线特征差异。与携带 AA 或 AG 基因型的患者（49.1%和 39.2%，p=0.01；52.4%和 40.1%，p=0.01；47.8%和 37.9%，p=0.04；分别）相比，携带 GG 基因型的 rs10757274、rs2383206 和 rs10757278 患者的糖尿病发生率较低。在 rs10757274、rs10757278 和 rs1333049 中观察到双血管和三血管疾病患者之间基因型频率的显著差异。最后，与 AA 和 AG 基因型相比，携带 rs2383206 的 GG 基因型患者的总死亡率更高（19.5%、11.9%、11.0%，分别；p=0.04）。此外，即使在调整 Cox 多变量模型以考虑年龄、既往心肌梗死、糖尿病、吸烟和冠状动脉解剖类型后，rs2383206 与总死亡率增加 1.75 倍的风险仍显著相关（p=0.02）。
结论
我们的数据与之前的证据一致，即染色体 9p21 遗传变异可能在不同情况下构成心血管系统的遗传调节剂。在患有明确 CAD 的患者中，我们观察到 rs2383206 与多血管 CAD 患者总死亡率和心脏原因死亡发生率升高之间存在关联。
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