PPM1A Methylation Is Associated With Vascular Recurrence in Aspirin-Treated Patients

C Gallego-Fabrega, C Carrera, JL Reny, P Fontana… - Stroke, 2016 - Am Heart Assoc
C Gallego-Fabrega, C Carrera, JL Reny, P Fontana, A Slowik, J Pera, A Pezzini
Stroke, 2016Am Heart Assoc
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 450 000 methylation sites were …
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 450 000 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=9.69×10−06, RAF1), cg04985020 (P=3.47×10−03, PPM1A), and cg08419850 (P=3.47×10−03, KCNQ1). Joint analysis identified an epigenome-wide association for cg04985020 (PPM1A; P=1.78×10−07), 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.
Am Heart Assoc