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Long noncoding RNAs (lncRNAs) serve as regulators or effectors of the p53 regulatory pathway. The lncRNA-p53 regulatory network plays an important role in ischemia-induced apoptosis and may be important for post-stroke recovery. Eight genetic variants of p53-related lncRNAs were genotyped in 982 patients to explore the association of single nucleotide polymorphisms (SNPs) in the genes related to the p53 regulatory pathway with ischemic stroke (IS) prognosis in a northern Chinese population. Long- and short-term outcomes were assessed by stroke recurrence and modified Rankin Scale score 3 months after stroke, respectively. We first identified that p53 rs1042522 and LINC-ROR rs2027701 could be associated with IS recurrence risk. On further cumulative effect analysis, we found that these two polymorphisms could jointly be associated with IS recurrence. Patients carrying 2-4 risk alleles showed a significantly higher IS recurrence risk than those harboring no or a single risk allele. In contrast to rs2027701 and rs1042522, the other SNPs were not associated with IS recurrence. Subsequently, we found that TUG1 rs2240183 CC genotype was associated with a favorable IS outcome after adjusting for confounding factors. However, the other seven genetic variants of p53-related lncRNAs were not associated with a functional outcome after stroke. p53 rs1042522 and LINC-ROR rs2027701 may exert combined effects on IS recurrence, and TUG1 rs2240183 may be a new biomarker to predict short-term IS outcomes as it modulates p53-mediated apoptosis.

Association Between Genetic Variants in the lncRNA–p53 Regulatory Network and Ischemic Stroke Prognosis