Construction and validation of a multi-mRNA panel and genetic scores for Krüppel-like factors for acute ischemic...

Cellular and animal experiments suggest that Krϋppel-like factors (KLFs) may be involved in the pathological mechanisms of acute ischemic stroke (AIS), but epidemiological research on KLFs in AIS is still limited. Therefore, we conducted two AIS case-control studies, and three prospective cohort studies to elucidate the contribution of 14 KLFs' distinct leukocytes mRNA expression (360 AIS cases vs. 363 controls) and 21 genetic tagSNPs (3651 AIS cases vs. 3900 controls) to the etiology and prognosis of AIS. We found KLFs mRNA score constructed by differentially expressed mRNAs significantly enhances the discriminative value for AIS compared to the traditional risk factors [the area under the curve (AUC) increased from 0.724 to 0.871]. Additionally, the KLFs polygenetic risk score could effectively stratify the susceptibility to AIS incidence (P_trend < 0.001) and the highest PRS group has an increased 42.4 % risk of AIS onset in the cohort study. Furthermore, KLF12 mRNA negatively related to modified Rankin Scale (mRS) both at admission and discharge and KLF12 variants contributed to an elevated risk of IS death after AIS. In conclusion, this study provides new insights into the novel contribution of KLFs mRNA and genetic variants to the incidence risk and prognosis of AIS.