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

Israel Fernández-Cadenas, Maite Mendióroz, Dolors Giralt, Cristina Nafria, Elena Garcia, Caty Carrera, Cristina Gallego-Fabrega, Sophie Domingues-Montanari, Pilar Delgado, Marc Ribó, Mar Castellanos, Sergi Martínez, Marimar Freijo, Jordi Jiménez-Conde, Marta Rubiera, José Alvarez-Sabín, Carlos A. Molina, Maria Angels Font, Marta Grau Olivares, Ernest PalomerasNatalia Perez De La Ossa, Maite Martinez-Zabaleta, Jaime Masjuan, Francisco Moniche, David Canovas, Carlos Piñana, Francisco Purroy, Dolores Cocho, Inma Navas, Carlos Tejero, Nuria Aymerich, Natalia Cullell, Elena Muiño, Joaquín Serena, Francisco Rubio, Antoni Davalos, Jaume Roquer, Juan Francisco Arenillas, Joan Martí-Fábregas, Keith Keene, Wei Min Chen, Bradford Worrall, Michele Sale, Adrià Arboix, Jerzy Krupinski, Joan Montaner

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8 Citations (Scopus)

Abstract

© 2017 American Heart Association, Inc. 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=9×10-03), 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.
Original languageEnglish
Pages (from-to)1147-1153
JournalStroke
Volume48
Issue number5
DOIs
Publication statusPublished - 1 May 2017

Keywords

  • genetics
  • ischemic attack
  • recurrence
  • risk factors
  • stroke
  • transient

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    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, C. A., Font, M. A., Grau Olivares, M., ... Montaner, J. (2017). GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to Predict the Vascular Recurrence after Stroke. Stroke, 48(5), 1147-1153. https://doi.org/10.1161/STROKEAHA.116.014322