Genetic Variation at the Quaking Locus Associates with Clinical Restenosis after Percutaneous Coronary Intervention and Induces Vascular Smooth Muscle Cell Dysfunction

摘要: The mRNA binding protein Quaking (Qk) has been implicated in embryonic vasculogenesis, which is primarily dependent on vascular smooth muscle cell (VSMC) differentiation, but a role adulthood remains elusive. Restenosis frequent complication of percutaneous coronary intervention (PCI) and mainly VSMC proliferation migration. Therefore, we hypothesized that single nucleotide polymorphisms (SNPs) the Qk gene could have profound impact mediated restenosis humans may serve as markers for risk stratification. GENetic DEterminants (GENDER) project multicenter, prospective study design enrolled 3,104 consecutive patients after successful PCI. We set out to characterize instent by analysis association 12 SNPs throughout restenosis. As many seven were found significantly associate with target vessel revascularization (TVR). strongest associations close transcription start site (2786 T/C: HR: 2.3, 95%CI: 1.3–3.9, P=0.002) intron 3 (57896 A/G: 0.7, 0.6 – 0.9, P=0.005 65752 1.5, 1.1–1.9, P=0.006). Ten percent carried 65752G allele lacked protective 57896G allele. Importantly, these at high develop (HR: 1.8, 1.3–2.5, p v ) mice versus wild type littermates. VSMCs derived from characterized stellate morphology, displayed decreased capacity deal serum withdrawal-induced stress. are first identify link altered VMSC differentiation deficient suggests causal relationship, marker TVR prediction therapeutic target.