GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to Predict the Vascular Recurrence After Stroke.
GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to Predict the Vascular Recurrence After Stroke.
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DOI：
10.1161/strokeaha.116.014322
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发表时间：
2017-05
期刊：
影响因子：
8.3
通讯作者：
GRECOS Study Group
中科院分区：
文献类型：
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作者：
Fernández-Cadenas I;Mendióroz M;Giralt D;Nafria C;Garcia E;Carrera C;Gallego-Fabrega C;Domingues-Montanari S;Delgado P;Ribó M;Castellanos M;Martínez S;Freijo M;Jiménez-Conde J;Rubiera M;Alvarez-Sabín J;Molina CA;Font MA;Grau Olivares M;Palomeras E;Perez de la Ossa N;Martinez-Zabaleta M;Masjuan J;Moniche F;Canovas D;Piñana C;Purroy F;Cocho D;Navas I;Tejero C;Aymerich N;Cullell N;Muiño E;Serena J;Rubio F;Davalos A;Roquer J;Arenillas JF;Martí-Fábregas J;Keene K;Chen WM;Worrall B;Sale M;Arboix A;Krupinski J;Montaner J;GRECOS Study Group
11%的患者在缺血性中风(IS)或短暂性脑缺血发作(TIA)后的第一年内发生血管复发。临床评分不能预测整个血管复发的风险，因此我们的目标是寻找与复发相关的遗传变异，以改善IS的临床预测模型。我们分析了3个患者队列中115个候选基因的256个多态性，这些患者包括4,482名IS或TIA患者。这一发现队列是前瞻性招募的，包括1,494名患者，其中6.2%的患者在第一年的随访中出现了新的IS。使用SNPlex或HumanOmni1-Quad技术对2988名患者进行了复制分析。我们使用COX回归(Grecs评分)生成预测模型，并使用分类树方法生成风险组。分析表明，动脉钙化相关基因Mgp的rs1800801(HR：1.33，p=9×10−03)在第1年的随访中与新发的IS相关。该多态性在西班牙队列(n=1.305)中被复制，但在北美队列(n=1.683)中没有显著相关性。Grecs评分预测了新的IS(p=3.2x10−09)，并可以将患者从低风险中风复发(1.9%)到高风险中风复发(12.6%)进行分类。此外，与以前的SPI-II评分相比，在Grecs评分中加入遗传风险因素改善了预测(p=0.03)。遗传学的应用可能有助于估计IS后血管复发的风险。在西班牙人群中，MGP基因的遗传变异与血管复发有关。
Vascular recurrence occurs in 11% of patients during the first year after ischemic stroke (IS) or transient ischemic attack (TIA). Clinical scores do not predict the whole vascular recurrence risk, therefore we aimed to find genetic variants associated with recurrence that might improve the clinical predictive models in IS. We analyzed 256 polymorphisms from 115 candidate genes in three patient cohorts comprising 4,482 IS or TIA patients. The discovery cohort was prospectively recruited and included 1,494 patients, 6.2% of them developed a new IS during the first year of follow-up. Replication analysis was performed in 2,988 patients using SNPlex or HumanOmni1-Quad technology. We generated a predictive model using Cox regression (GRECOS score), and generated risk groups using a classification tree method. The analyses revealed that rs1800801 in the MGP gene (HR: 1.33, p= 9×10−03), a gene related to artery calcification, was associated with new IS during the first year of follow-up. This polymorphism was replicated in a Spanish cohort (n=1.305), however it was not significantly associated in a North American cohort (n=1.683). The GRECOS score predicted new IS (p= 3.2×10−09) and could classify patients, from low risk of stroke recurrence (1.9%) to high risk (12.6%). Moreover, the addition of genetic risk factors to the GRECOS score improves the prediction compared to previous SPI-II score (p=0.03). The use of genetics could be useful to estimate vascular recurrence risk after IS. Genetic variability in the MGP gene was associated with vascular recurrence in the Spanish population.