GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to Predict the Vascular Recurrence After Stroke

BACKGROUND AND PURPOSE—Vascular recurrence occurs in 11% of patients during the first year after ischemic stroke (IS) or transient ischemic attack. Clinical scores do not predict the whole vascular recurrence risk; therefore, we aimed to find genetic variants associated with recurrence that might im...

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Bibliographic Details
Published in:Stroke (1970) 2017-05, Vol.48 (5), p.1147-1153
Main Authors: 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
Format: Article
Language:English
Subjects:
Aged
Brain Ischemia - diagnosis
Brain Ischemia - genetics
Cardiovascular Diseases - diagnosis
Cardiovascular Diseases - genetics
Cohort Studies
Female
Genotype
Humans
Ischemic Attack, Transient - diagnosis
Ischemic Attack, Transient - genetics
Male
North America
Polymorphism, Single Nucleotide
Prognosis
Recurrence
Risk
Scotland
Spain
Stroke - diagnosis
Stroke - genetics
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Summary:BACKGROUND AND PURPOSE—Vascular recurrence occurs in 11% of patients during the first year after ischemic stroke (IS) or transient ischemic attack. 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. 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), 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) 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.
ISSN:0039-2499
1524-4628
DOI:10.1161/STROKEAHA.116.014322