DNase1 RS1053874 Polymorphism is Associated with Early Neurological Recovery through NET Modulation and with...

Area of Science:

• Cardiovascular Sciences
• Genetics
• Neurology

Background:

• Immunothrombosis, involving neutrophil extracellular traps (NETs), plays a key role in ischemic stroke.
• DNase1 degrades NETs, and its rs1053874 polymorphism may affect NET formation and stroke outcomes.
• The clinical impact of the DNase1 rs1053874 variant in ischemic stroke is currently unknown.

Purpose of the Study:

• To investigate if the DNase1 rs1053874 polymorphism influences systemic NET burden.
• To determine the association between this genetic variant and clinical outcomes in patients with acute ischemic stroke.

Main Methods:

• A prospective observational cohort study of 492 acute ischemic stroke patients.
• Genotyping of the DNase1 rs1053874 polymorphism using Sanger sequencing.
• Assessment of clinical variables, NET biomarkers, DNase1 activity, infarct volume, thrombectomy metrics, and survival, analyzed with regression and Cox models.

Main Results:

• AA genotype carriers (7.9%) showed higher DNase1 activity and lower NET markers, neutrophils, and monocytes compared to GG+GA carriers.
• AA genotype was associated with fewer thrombectomy passes, better early neurological recovery, and smaller infarct volumes.
• The AA genotype and dyslipidemia were independently linked to improved long-term survival, with the strongest benefit seen in AA carriers without dyslipidemia.

Conclusions:

• The DNase1 rs1053874 polymorphism impacts NET-related inflammation and is linked to an improved vascular profile and better outcomes in ischemic stroke.
• These findings highlight DNase1 as a potential therapeutic and prognostic target for personalized stroke management.
• The study suggests that genetic variations in DNase1 could influence individual responses to stroke and treatment strategies.