Single nucleotide polymorphisms (SNPs) in patients with acute ischemic stroke: A prospective study of the relationship between genetic, acute phase cytokine levels and stroke prognosis

Abstract

The genetic basis of complex diseases like ischemic stroke probably consists of several predisposing risk factors, such as genes involved in inflammation and thrombotic pathways. Some genetic polymorphisms have been associated with the risk of stroke.
Aim: On this basis the aim of this study was to evaluate:
- the frequency of some single nucleotide polymorphisms (SNPs) of genes of pro-inflammatory cytokines and coagulation factors in stroke patients;
- the relationship between each identified SNP and TOAST stroke subtype;
- the relationship between the serum levels of the cytokines analyzed and the diagnostic subtype of ischemic stroke;
- the relationship between the serum levels of the analyzed cytokines and stroke prognosis regarding event recurrence, AMI recurrence, and mortality.
Materials and methods: All patients aged > 18 years admitted for acute ischemic stroke in the period between 2011 and 2021 were prospectively enrolled. Each patient was subjected to genetic analysis to evaluate various genetic polymorphisms and to the analysis of the levels of cytokines circulating in the different collection times (T0, T1, and T2). Three different biallelic polymorphisms, of the IL-10 gene were identified.
Results: 624 subjects were enrolled, including 429 patients with ischemic stroke and 195 controls. Stroke subtype: 47% LAAS, 27% LAC, and 26% CEI. Regarding the immunoinflammatory variables, patients with CEI showed significantly higher levels of serum glucose and all the cytokines analyzed, compared to patients with both LAC and LAAS.
Logistic regression analysis revealed that elevated IL-10, TNF-alpha, IL-6, and IL-1beta values are predictive of LAAS and CEI subtypes, respectively. IL-10 levels were lower in patients who developed stroke during follow-up, whereas TNF-alpha, IL-1, and IL-6 levels were significantly higher in patients with recurrent stroke at follow-up, who developed a new vascular event or who experienced death during follow-up. From the analysis of the distribution of the genotypic frequencies of the polymorphisms analyzed, a statistically significant difference emerged between the cases and the controls for all the polymorphisms in the genes of pro-inflammatory cytokines, TPA and PAI-1.
These results demonstrated an association between some pro-inflammatory and prothrombotic polymorphisms and the risk of ischemic stroke.