Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN, USA.
BMC Med Genet. 2014 Jun 6;15:66. doi: 10.1186/1471-2350-15-66.
Studies suggest that the 9p21-3 locus may influence susceptibility to myocardial infarction. We performed a systematic review and meta-analysis to assess whether this locus is associated with severity of coronary atherosclerosis and adverse clinical outcomes in those with known coronary disease.
Multiple electronic databases were searched from inception through August 2012. Studies examining 9p21-3 genotype in patients with known coronary artery disease were included. We extracted the association of the 9p21-3 locus with measures of severity of coronary atherosclerosis [number of diseased vessels, Gensini Score, Duke CAD Prognostic Index (DPI)], angiographic outcomes [change in minimum lumen diameter (∆MLD) and number of new lesions at follow-up], and key clinical outcomes (all-cause mortality, recurrent myocardial infarction and the need for coronary revascularization). Relative risks (RR) and weighted mean difference (WMD) were pooled using the random effects models.
23 cohorts enrolling 16,860 participants were analyzed. There was no significant difference between HR and LR genotypes in terms of all-cause mortality, recurrent myocardial infarction or the frequency of coronary revascularization. HR genotype was associated with increased risk of triple vessel disease (RR = 1.34; 95% CI 1.08-1.65; P = 0.01) and increased baseline Gensini Score (WMD = 5.30; 95% CI 0.66-9.93; P = 0.03). However there was no association with DPI (WMD = 4.00; 95% CI 2.94-10.94; P = 0.26). HR genotype did not predict ∆MLD or number of new lesions at follow-up.
Patients of coronary atherosclerosis who carry the high risk genotype of the 9p21-3 allele may be more likely to have multi-vessel CAD. However the effect of this allele on CAD progression and disease specific clinical outcomes are not observed possibly due to diminishing genetic risk following dietary modification and therapy.
研究表明 9p21-3 基因座可能影响心肌梗死的易感性。我们进行了系统评价和荟萃分析，以评估该基因座与已知冠心病患者的冠状动脉粥样硬化严重程度和不良临床结局是否相关。
从建库到 2012 年 8 月，我们检索了多个电子数据库。包括了研究已知冠状动脉疾病患者 9p21-3 基因型的患者。我们提取了 9p21-3 基因座与冠状动脉粥样硬化严重程度的相关性指标[病变血管数量、Gensini 评分、杜克 CAD 预后指数（DPI）]、血管造影结果[最小管腔直径的变化（∆MLD）和随访时新病变的数量]以及关键临床结局（全因死亡率、复发性心肌梗死和需要冠状动脉血运重建）的相关性。使用随机效应模型汇总相对风险（RR）和加权均数差（WMD）。
分析了 23 项纳入 16860 名参与者的队列研究。在全因死亡率、复发性心肌梗死或冠状动脉血运重建的频率方面，HR 和 LR 基因型之间没有显著差异。HR 基因型与三血管疾病的风险增加相关（RR=1.34；95%CI 1.08-1.65；P=0.01），且基线 Gensini 评分较高（WMD=5.30；95%CI 0.66-9.93；P=0.03）。然而，DPI 与 HR 基因型没有相关性（WMD=4.00；95%CI 2.94-10.94；P=0.26）。HR 基因型也不能预测 ∆MLD 或随访时新病变的数量。
患有冠状动脉粥样硬化的患者携带 9p21-3 等位基因的高危基因型，可能更容易患多血管 CAD。然而，由于饮食和治疗后遗传风险降低，该等位基因对 CAD 进展和特定疾病的临床结局没有影响。
