PPM1A Methylation Is Associated With Vascular Recurrence in Aspirin-Treated Patients
Por:
Gallego-Fabrega, C, Carrera, C, Reny, JL, Fontana, P, Slowik, A, Pera, J, Pezzini, A, Serrano-Heras, G, Segura, T, Bin Dukhyil, AAA, Marti-Fabregas, J, Muino, E, Cullell, N, Montaner, J, Krupinski, J, Fernandez-Cadenas, I
Publicada:
1 jul 2016
Resumen:
Background and Purpose-Despite great efforts by pharmacogenetic studies, the causes of aspirin failure to prevent the recurrence of ischemic events remain unclear. Our aim was to study whether epigenetics could be associated with the risk of vascular recurrence in aspirin-treated stroke patients.
Methods-We performed an epigenetic joint analysis study in 327 patients treated with aspirin. In the discovery stage, we performed a nested case-control study in 38 matched ischemic stroke patients in whom 450000 methylation sites were analyzed. Nineteen patients presented vascular recurrence after stroke, and 19 matched patients did not present vascular recurrence during the first year of follow-up. In a second stage, 289 new patients were analyzed by EpiTYPER.
Results-The following 3 differentially methylated candidate CpG sites, were identified in the discovery stage and analyzed in the second stage: cg26039762 (P=9.69x10(-06), RAF1), cg04985020 (P=3.47x10(-03), PPM1A), and cg08419850 (P=3.47x10(-03), KCNQ1). Joint analysis identified an epigenome-wide association for cg04985020 (PPM1A; P=1.78x10(-07)), with vascular recurrence in patients treated with aspirin.
Conclusions-The pattern of differential methylation in PPM1A is associated with vascular recurrence in aspirin-treated stroke patients.
Filiaciones:
Gallego-Fabrega, C:
Hosp Mutua Terrassa, Fdn Docencia & Recerca MutuaTerrassa, Stroke Pharmacogenom & Genet, Terrassa, Spain
Univ Barcelona, Sch Med, Barcelona, Spain
Carrera, C:
Univ Autonoma Barcelona, Vall Hebron Inst Res, Neurovasc Res Lab, Barcelona, Spain
Reny, JL:
Univ Hosp Geneva, Div Internal Med & Rehabil, Geneva, Switzerland
Fac Med, Geneva Platelet Grp, Geneva, Switzerland
Fontana, P:
Univ Hosp Geneva, Div Angiol & Haemostasis, Geneva, Switzerland
Fac Med, Geneva Platelet Grp, Geneva, Switzerland
Slowik, A:
Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland
Pera, J:
Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland
Pezzini, A:
Univ Brescia, Dipartimento Sci Cliniche & Sperimentali, Clin Neurolog, Brescia, Italy
Serrano-Heras, G:
Albacete Hosp, Dept Neurol, Albacete, Spain
Segura, T:
Albacete Hosp, Dept Neurol, Albacete, Spain
Bin Dukhyil, AAA:
Majmaah Univ, Coll Appl Med Sci, Acad City, Al Majmaah, Saudi Arabia
Marti-Fabregas, J:
Hosp Santa Creu & Sant Pau, IIB St Pau, Dept Neurol, Barcelona, Spain
Muino, E:
Hosp Mutua Terrassa, Fdn Docencia & Recerca MutuaTerrassa, Stroke Pharmacogenom & Genet, Terrassa, Spain
Cullell, N:
Hosp Mutua Terrassa, Fdn Docencia & Recerca MutuaTerrassa, Stroke Pharmacogenom & Genet, Terrassa, Spain
Montaner, J:
Univ Autonoma Barcelona, Vall Hebron Inst Res, Neurovasc Res Lab, Barcelona, Spain
Krupinski, J:
Hosp Univ Mutua Terrassa, Neurol Serv, Terrassa, Spain
Manchester Metropolitan Univ, Sch Healthcare Sci, Manchester, Lancs, England
Fernandez-Cadenas, I:
Hosp Mutua Terrassa, Fdn Docencia & Recerca MutuaTerrassa, Stroke Pharmacogenom & Genet, Terrassa, Spain
Open Access
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