An Inflammatory Polymorphisms Risk Scoring System for the Differentiation of Ischemic Stroke Subtypes

Area of Science:

• Genetics
• Inflammation
• Neurology

Background:

• Inflammation is implicated in atherothrombotic and cardioembolic stroke.
• Genetic risk factors differ among ischemic stroke subtypes (cardioembolic, atherothrombotic, lacunar).
• No prior studies developed genetic risk scores for stroke subtypes using inflammation-associated polymorphisms.

Purpose of the Study:

• To create and validate a genetic risk scoring system for ischemic stroke subtypes based on inflammation-associated polymorphisms.
• To investigate the association between inflammation genetics and specific ischemic stroke subtypes.

Main Methods:

• Analyzed 68 polymorphisms in 30 inflammatory mediator genes in 2,685 subjects (1,987 stroke cases, 698 controls).
• Developed a genetic scoring system weighting significant polymorphisms by odds ratio, considering stroke subtype.
• Validated the genetic score in an independent cohort.

Main Results:

• Three polymorphisms (rs1205 in CRP, rs1800779 and rs2257073 in NOS3) associated with cardioembolic stroke (p < 0.05).
• The generated genetic risk score significantly associated with cardioembolic stroke (p=0.001) and replicated (p=0.017).
• Individuals with the highest genetic score had a 92.2% probability of cardioembolic stroke (p=0.002).

Conclusions:

• Inflammatory marker genetics show a stronger association with cardioembolic stroke than atherothrombotic or lacunar stroke.
• The developed genetic risk scoring system shows potential for predicting and differentiating ischemic stroke, particularly cardioembolic subtype.
• The genetic risk score's specificity to cardioembolic stroke subtypes requires further investigation.