GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to Predict the Vascular Recurrence After Stroke.
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Fernández-Cadenas Israel, Mendióroz Maite, Giralt Dolors, Nafria Cristina, Garcia Elena, Carrera Caty, Gallego-Fabrega Cristina, Domingues-Montanari Sophie, Delgado Pilar, Ribó Marc, Castellanos Mar, Martínez Sergi, Freijo Marimar, Jiménez-Conde Jordi, Rubiera Marta, Alvarez-Sabín José, Molina Carlos A, Font Maria Angels, Grau Olivares Marta, Palomeras Ernest, Perez de la Ossa Natalia, Martinez-Zabaleta Maite, Masjuan Jaime, Moniche Francisco, Canovas David, Piñana Carlos, Purroy Francisco, Cocho Dolores, Navas Inma, Tejero Carlos, Aymerich Nuria, Cullell Natalia, Muiño Elena, Serena Joaquín, Rubio Francisco, Davalos Antoni, Roquer Jaume, Arenillas Juan Francisco, Martí-Fábregas Joan, Keene Keith, Chen Wei-Min, Worrall Bradford, Sale Michele, Arboix Adrià, Krupinski Jerzy, Montaner Joan, GRECOS Study Group
Аннотация
METHODS: We analyzed 256 polymorphisms from 115 candidate genes in 3 patient cohorts comprising 4482 IS or transient ischemic attack patients. The discovery cohort was prospectively recruited and included 1494 patients, 6.2% of them developed a new IS during the first year of follow-up. Replication analysis was performed in 2988 patients using SNPlex or HumanOmni1-Quad technology. We generated a predictive model using Cox regression (GRECOS score [Genotyping Reurrence Risk of Stroke]) and generated risk groups using a classification tree method.
RESULTS: The analyses revealed that rs1800801 in the MGP gene (hazard ratio, 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 with previous Stroke Prognosis Instrument-II score (P=0.03).
CONCLUSIONS: 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.