From the Journals

Genetic variants may predict stroke in some adult SCD populations



Oxidative stress-related genetic variants may provide a simple and inexpensive alternative for identifying patients with sickle cell disease at risk of stroke, according to an analysis presented in the Journal of the Neurological Sciences.

The multicenter study reviewed 499 unrelated patients with sickle cell anemia aged > 18 years who were genotyped and assessed for stroke incidence.

Patient follow-up was 26 years and was last updated in January 2018. The median age of the cohort was 31 years, with 223 men (45%), and clinical outcomes were similar between the Brazilian centers studied. Primary stroke was confirmed in 35 patients (7%) using medical records, and all primary strokes were confirmed by baseline brain magnetic resonance imaging. The remaining 464 patients were free of clinical stroke during the entire study, according to Igor F. Domingos of the Genetics Postgraduate Program, Federal University of Pernambuco, Recife, Brazil, and colleagues.

All patients were fully genotyped for five candidate variants in the SOD2, GPX3, and CAT01 genes, along with alpha-thalassemia status and beta-globin gene haplotypes. In univariate logistic regression analysis, the SOD2 Val16Ala polymorphism was significantly associated with risk of stroke (odds ratio [OR]: 2.51; 95% confidence interval [CI]: 1.49-4.23; P = .001), and was consistent with the results of multivariate analysis: (OR: 1.98, 95% CI, 1.18-3.32; P = .009). The estimated long-term cumulative incidence of stroke at 10 years was 5% (95% CI: 3-8%).

Proportional hazards regression analysis also showed that SOD2 Val16Ala polymorphism was associated with risk of stroke in both univariate (hazard ratio [HR]: 2.22, 95% CI:1.36–3.63; P = .001) and multivariate analyses (HR: 2.24, 95% CI:1.3–3.9; P = .004).

However, a validation cohort of 231 patients regularly followed at King’s College London for whom biological samples were available did not show similar results. Overall, 32 patients (14%) had a stroke and SOD2 Val16Ala polymorphism was found to have no association with stroke in the independent validation cohort (P = .494),

The authors cautioned that their data may be influenced by unique genetic differences between the Brazilian sickle cell patients and other populations and that they did not have imaging data on the control group, so were unable to detect the possibility of silent infarcts.

“Although we recognize that select a group of patients for heightened vigilance based on a single polymorphism is premature, we believe that the use of genetic modifiers may provide an option for identifying patients at stroke risk,” the authors stated.

The authors reported that they had no competing financial interests.

SOURCE: ADomingos IF et al. J Neurologic Sciences. 2020;

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