GRECOS Project (Genotyping Recurrence Risk of Stroke)

Author:

Fernández-Cadenas Israel1,Mendióroz Maite1,Giralt Dolors1,Nafria Cristina1,Garcia Elena1,Carrera Caty1,Gallego-Fabrega Cristina1,Domingues-Montanari Sophie1,Delgado Pilar1,Ribó Marc1,Castellanos Mar1,Martínez Sergi1,Freijo Marimar1,Jiménez-Conde Jordi1,Rubiera Marta1,Alvarez-Sabín José1,Molina Carlos A.1,Font Maria Angels1,Grau Olivares Marta1,Palomeras Ernest1,Perez de la Ossa Natalia1,Martinez-Zabaleta Maite1,Masjuan Jaime1,Moniche Francisco1,Canovas David1,Piñana Carlos1,Purroy Francisco1,Cocho Dolores1,Navas Inma1,Tejero Carlos1,Aymerich Nuria1,Cullell Natalia1,Muiño Elena1,Serena Joaquín1,Rubio Francisco1,Davalos Antoni1,Roquer Jaume1,Arenillas Juan Francisco1,Martí-Fábregas Joan1,Keene Keith1,Chen Wei-Min1,Worrall Bradford1,Sale Michele1,Arboix Adrià1,Krupinski Jerzy1,Montaner Joan1

Affiliation:

1. From the Stroke Pharmacogenomics and Genetics, Fundacio Docència i Recerca MutuaTerrassa, Spain (I.F.-C., E.G., C.G.-F., N.C., E.M.); Neurovascular Research Laboratory and Neurovascular Unit, Neurology and Medicine Departments-Universitat Autònoma de Barcelona (I.F.-C., M.M., D.G., C.N., C.C., S.D.-M., P.D., J.M.) and Neurology Department (M.Ribó, M.Rubiera, J.A.-S., C.A.M.), Vall d’Hebron Hospital, Barcelona, Spain; Neuroepigenetics Research Group, Navarrabiomed, Pamplona, Spain (M.M.); Department...

Abstract

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Advanced and Specialized Nursing,Cardiology and Cardiovascular Medicine,Neurology (clinical)

Reference28 articles.

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