Abstract
BACKGROUND: Stent thrombosis (ST) is a rare, yet devastating, complication following percutaneous coronary intervention (PCI), with poorly understood pathophysiologic characteristics and genetic backgrounds. OBJECTIVES: The authors performed a genome-wide association study to identify the common genetic loci associated with early stent thrombosis (EST) and late/very late ST (LST/VLST) in a contemporary Japanese multicenter PCI registry. METHODS: Among 8,642 PCI patients included in the registry, 42 who experienced stent thrombosis [EST (n = 15) and LST/VLST (n = 27)] were included (mean age, 67.6 ± 10.8 years; and 88.1% men). We conducted a genome-wide association study using the BioBank Japan patient population as the control (control #1: acute coronary syndrome [n = 29,542] and control #2: effort angina [n = 8,900]) to identify significant single nucleotide polymorphisms (SNPs) and evaluate the performance of polygenic risk scores (PRSs) for predicting these conditions. RESULTS: We compared patients with EST with controls #1 and #2 and identified SNPs (rs565401593 and rs561634568) in NSD1, and patients with LST/VLST with controls #1 and #2 and identified SNPs (rs532623294 and rs199546342) in GRIN2A. PRS for LST/VLST showed high predictive performance (area under the curve 0.83 [95% CI: 0.76-0.89] and 0.83 [95% CI: 0.77-0.89]), whereas PRS for EST showed modest predictive performance (area under the curve 0.71 [95% CI: 0.58-0.85] and 0.72 [95% CI: 0.58-0.85]). CONCLUSIONS: We identified different genetic predispositions between EST and LST/VLST and demonstrated that the incorporation of PRS may aid in risk prediction of this highly fatal event.