Interactions among variants in P53 apoptotic pathway genes are associated with neurologic deterioration and functional outcome after acute ischemic stroke
| Autor: | Guo Sui, Qiang Zhou, Shaozhi Bao, Jie Li, Xingyang Yi, Gaoping Ren, Lili Tan, Jing Lin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
MDM‐2
medicine.medical_specialty Neurosciences. Biological psychiatry. Neuropsychiatry Outcome (game theory) 050105 experimental psychology Brain Ischemia 03 medical and health sciences Behavioral Neuroscience 0302 clinical medicine Modified Rankin Scale Risk Factors Internal medicine medicine ischemic stroke Neurologic deterioration genetic polymorphism Humans 0501 psychology and cognitive sciences Gene Stroke neurologic deterioration Original Research Univariate analysis P53 Multifactor dimensionality reduction MMP‐9 business.industry 05 social sciences Proto-Oncogene Proteins c-mdm2 medicine.disease Matrix Metalloproteinase 9 Apoptosis outcome Tumor Suppressor Protein p53 business 030217 neurology & neurosurgery RC321-571 |
| Zdroj: | Brain and Behavior Brain and Behavior, Vol 11, Iss 5, Pp n/a-n/a (2021) |
| ISSN: | 2162-3279 |
| Popis: | Objective Neurologic deterioration (ND) and functional outcome after ischemic stroke (IS) are not accurately predicted by clinical pictures on admission. The aim of present study was to investigate the association of variants in P53 apoptotic pathway genes with ND and functional outcome after IS. Methods Genotypes of nine variants in apoptosis‐relevant genes were measured in patients with acute IS. Gene–gene interactions were analyzed by generalized multifactor dimensionality reduction (GMDR). The primary outcome was ND. ND was diagnosed in patients who worsened ≥2 points (National Institutes of Health Stroke Scale [NIHSS] score) within the first 10 days of stroke onset. The secondary outcome was functional status at 90 days after IS as measured by modified Rankin Scale (mRS) score. Results A total of 705 enrolled patients, ND occurred in 174 (24.7%) patients, and 184 (26.1%) patients were poor functional outcome (mRS score > 2). Although the nine variants were not significantly associated with ND and functional outcome by univariate analysis, there was a gene–gene interaction among P53rs1042522, MDM‐2rs2279744, and MMP‐9 rs3918242 using GMDR analysis. The high‐risk interaction among the three variants was independently associated with higher risk of ND (HR, 2.04, 95% CI: 1.22–5.64, p = .018) and poor functional outcome (OR, 2.68, 95% CI: 1.68–7.86, p = .004) after adjusting for the covariates. Conclusion The interactions among P53 rs1042522, MDM‐2 rs2279744, and MMP‐9 rs3918242 may increase the risk of ND and poor functional outcome and may be considered as a genetic marker of predicting ND and poor functional outcome after stroke. (a) The neurologic deterioration (ND) and functional outcome after ischemic stroke (IS) are not accurately predicted by clinical pictures on admission. (b) There was a gene–gene interaction among P53 rs1042522, MDM-2 rs2279744, and MMP-9 rs3918242 using GMDR analysis. (c) The interactions among P53 rs1042522, MDM-2 rs2279744, and MMP-9 rs3918242 may increase the risk of ND and poor functional outcome and may be considered as a genetic marker predicting ND and poor functional outcome after stroke. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text