Evaluation of oxidative stress-related genetic variants for predicting stroke in patients with sickle cell anemia

Area of Science:

• Genetics
• Hematology
• Neurology

Background:

• Stroke is a significant cause of death and disability in adults with sickle cell anemia (SCA).
• Current stroke prediction strategies for adult SCA patients are limited, unlike in younger patients where transcranial Doppler ultrasonography is effective.
• Oxidative stress and genetic factors are implicated in the pathogenesis of ischemic brain injury in SCA.

Purpose of the Study:

• To investigate whether genetic variants associated with oxidative stress can predict stroke risk in adult patients with SCA.
• To identify specific genetic polymorphisms that correlate with stroke incidence in this population.

Main Methods:

• Genotyping of 499 adult SCA patients (>18 years) for specific polymorphisms: SOD2 Val16Ala (rs4880), GPX3 (rs8177404, rs8177406, rs8177412), and CAT01 (rs1001179).
• Analysis included α-thalassemia status and β-globin gene haplotypes.
• Statistical analysis to determine the association between genetic variants and stroke risk.

Main Results:

• The SOD2 Val16Ala polymorphism was significantly associated with an increased risk of stroke in adult SCA patients (OR: 1.98, 95% CI: 1.18-3.32, P=.009).
• This polymorphism was also independently associated with the long-term cumulative incidence of stroke (HR: 2.24, 95% CI: 1.3-3.9, P=.004).
• No significant association was found for the other tested GPX3 and CAT01 polymorphisms.

Conclusions:

• The SOD2 Val16Ala polymorphism is a potential biomarker for identifying adult SCA patients at higher risk of stroke.
• This genetic marker offers a simple, inexpensive, and alternative strategy for stroke risk assessment in SCA.
• Further research can validate these findings for clinical application in stroke prevention strategies.