ABSTRACT
OBJECTIVE@#To assess the influence of apolipoprotein E (ApoE) gene polymorphisms on the therapeutic effect of lipid-lowering statins in patients with ischemic cerebral infarction.@*METHODS@#One hundred and six patients with ischemic cerebral infarction who orally took lipid-lowering statins for 3 months were enrolled. Changes in serum triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) before and after the drug administration were analyzed. ApoE gene polymorphisms were detected by real-time fluorescent quantitative PCR, and genotypes of ApoE gene in patients with different effects were compared.@*RESULTS@#The detection rates for E2/E2, E2/E3, E3/E3, E2/E4 and E3/E4 genotypes were 0.94%, 11.32%, 63.21%, 1.89% and 22.64%, respectively. And the detection rates for E2, E3 and E4 alleles were 7.55%, 80.19% and 12.26%, respectively. Biochemical phenotypes included E2 type (13 cases, 12.26%), E3 type (69 cases, 65.09%) and E4 type (24 cases, 22.65%). Before administration, TG and TC of E2 type were the highest (P<0.05), but no significant difference was detected in HDL-C and LDL-C among the three phenotypes (P>0.05).Following the drug administration, TG, TC and LDL-C were decreased, while HDL-C was increased. HDL-C of E2 type was the highest, TC and LDL-C of E4 type were the highest (P<0.05). The E3/E3 ratio in low-efficiency group at admission was lower than that in the high-efficiency group, while the E3/E4 ratio was higher than that in the high-efficiency group (P<0.05). The proportion of E3 allele in low-efficiency group was lower than that in high-efficiency group, while the proportion of E4 allele was higher than that in high-efficiency group (P<0.05).@*CONCLUSION@#ApoE gene polymorphisms are closely correlated with the therapeutic effect of lipid-lowering statins in patients with ischemic cerebral infarction. The lipid-lowering effects are more significant in patients with E2 and E3 genotypes, but were poor in those with the E4 genotype. Personalized regimens should be applied.
Subject(s)
Humans , Apolipoproteins E/genetics , Cerebral Infarction/genetics , Genotype , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Lipids , Polymorphism, Genetic , TriglyceridesABSTRACT
Objective:To investigate the relationship between the activation level of Nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome and the change of cognitive functions in patients with acute ischemic stroke.Methods:A total of 88 patients with acute ischemic stroke in Department of Neurology from October 2018 to July 2020 were selected as case group and 100 healthy physical examinees were selected as control group.Peripheral blood of the case group and the control group was collected, and peripheral blood mononuclear cells (PBMCs) were isolated by centrifugation.Then the NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1 and interleukin-1β (IL-1β) expression were detected by Western blot.The cognitive function of patients with acute ischemic stroke was detected by Montreal Cognitive Assessment (MoCA). The differences in expression levels of NLRP3, ASC, Caspase-1 and IL-1β were compared between the case group and the control group.Pearson correlation analysis was used to analyze the correlation between expression levels of NLRP3, ASC, Caspase-1, IL-1β and MoCA score.Logistic multivariate regression was used to analyze the relationship between expression levels of NLRP3, ASC, caspase-1, IL-1β and the cognitive dysfunction.Results:(1)Western blot results showed that NLRP3, ASC, Caspase-1 and IL-1β expressions in PBMCs cells in the case group were higher than those in the control group (all P<0.05). (2)The expression level of NLRP3 in stroke patients with hypertension, hyperlipidemia, National Institutes of Health Stroke Scale (NIHSS) score ≥ 8 points was significantly higher than that in patients without hypertension, hyperlipidemia and NIHSS score<8 points ( P<0.05); (3)The incidence of cognitive dysfunction in the case group was 34.09% (30/88). The MoCA scores of the cognitive dysfunction group and the non-cognitive dysfunction group were 20 (24, 28) and 27 (26, 28) points respectively, and the difference between the groups was statistically significant ( P<0.05); (4)Pearson correlation analysis showed that NLRP3, ASC, caspase-1 and IL-1β expression in PBMCs cells were negatively correlated with MoCA scores ( r=-0.426, -0.396, -0.417, -0.320 respectively, all P<0.05). (5)Logistic regression analysis showed that hyperlipidemia, NIHSS scores, frontotemporal lobe infarction, and NLRP3 expression were the influencing factors for the occurrence of cognitive dysfunction (all P<0.05). Conclusion:Patients with acute ischemic stroke have high activated NLRP3 inflammasome, and its activation degree is closely related to the condition and the occurrence of cognitive dysfunction after stroke.Targeted inhibition or regulation of NLRP3 inflammasome activation may become a new idea of neuroprotection for acute ischemic stroke.