Construction and validation of a multi-mRNA panel and genetic scores for Krüppel-like factors for acute ischemic stroke
1Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Related Experiment Videos
View abstract on PubMed
Summary
Krüppel-like factors (KLFs) show promise in predicting acute ischemic stroke (AIS) risk and outcomes. KLF mRNA and genetic variants significantly contribute to AIS incidence and prognosis, offering new diagnostic and therapeutic insights.
Area of Science:
- Molecular Biology
- Genetics
- Neurology
Background:
- Cellular and animal studies suggest Krüppel-like factors (KLFs) role in acute ischemic stroke (AIS) pathology.
- Epidemiological research on KLFs in AIS etiology and prognosis remains limited.
Purpose of the Study:
- To investigate the contribution of 14 KLFs' leukocyte mRNA expression and 21 genetic tag single nucleotide polymorphisms (tagSNPs) to AIS.
- To evaluate KLFs' role in AIS incidence and patient outcomes.
Main Methods:
- Conducted two case-control studies and three prospective cohort studies involving 360 AIS cases and 363 controls for mRNA analysis.
- Analyzed 21 genetic tagSNPs in 3651 AIS cases and 3900 controls.
- Constructed KLFs mRNA and polygenic risk scores (PRS) to assess discriminative and stratification values.
Main Results:
- A KLFs mRNA score significantly improved AIS discrimination (AUC from 0.724 to 0.871).
- KLFs PRS effectively stratified AIS susceptibility (P<sub>trend</sub> < 0.001), with the highest PRS group showing a 42.4% increased AIS risk.
- KLF12 mRNA correlated negatively with modified Rankin Scale (mRS) scores, and KLF12 variants increased AIS-related death risk.
Conclusions:
- KLFs mRNA expression and genetic variants are novel contributors to AIS incidence and prognosis.
- KLFs offer potential as biomarkers for AIS risk stratification and outcome prediction.
- This study provides new insights into the etiological and prognostic roles of KLFs in AIS.