Evaluation of oxidative stress-related genetic variants for predicting stroke in patients with sickle cell anemia
| Autor: | Taciana Furtado de Mendonça, Stephan Menzel, Fernando Ferreira Costa, John N. Brewin, Anderson F. Cunha, Betania Lucena Domingues Hatzlhofer, Rayssa L. Borges-Medeiros, Antonio R. Lucena-Araujo, Evandra Strazza Rodrigues, Simone Kashima, Pedro Rodrigues Souza Cruz, Aderson S Araujo, Igor de Farias Domingos, Diego Arruda Falcão, Kate Gardner, Ana Claudia Mendonça dos Anjos, Maria do Socorro de Mendonça Cavalcanti, Diego A Pereira-Martins, Mônica Barbosa de Melo, Marcos André Cavalcanti Bezerra |
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| Rok vydání: | 2019 |
| Předmět: |
Oncology
Adult medicine.medical_specialty Ultrasonography Doppler Transcranial Anemia Sickle Cell 03 medical and health sciences 0302 clinical medicine alpha-Thalassemia Polymorphism (computer science) Internal medicine Medicine Humans Cumulative incidence 030212 general & internal medicine Stroke Aged business.industry Hazard ratio Haplotype Odds ratio medicine.disease Sickle cell anemia Confidence interval Oxidative Stress Neurology Neurology (clinical) business 030217 neurology & neurosurgery |
| Zdroj: | Journal of the neurological sciences. 414 |
| ISSN: | 1878-5883 |
| Popis: | Overt stroke in adults with sickle cell anemia (SCA) continues to be a major cause of morbidity and mortality, while no evidence-based strategy for prevention has been reached so far. Although transcranial Doppler ultrasonography represents the most important tool for identifying young patients with SCA at risk of primary stroke, strategies for stroke prediction in adulthood remain challenging. Emerging data suggest that oxidative stress may exert a pivotal role in the pathogenesis of ischemic brain injury. Combining these pieces of evidences with the well-known genetic contribution to the development of stroke in SCA, we hypothesized that genetic variants related to the biology of oxidative stress could be used to identify adult patients at higher risk of stroke. Overall, 499 unrelated patients with SCA aged >18 years were genotyped for SOD2 Val16Ala (rs4880), GPX3 T-568C (rs8177404), GPX3 T-518C (rs8177406), GPX3 T-65C (rs8177412), and CAT01 C-262 T (rs1001179) polymorphisms, along with α-thalassemia status and β-globin gene haplotypes. Of these, only the SOD2 Val16Ala polymorphism was associated with stroke. SOD2 Val16Ala polymorphism was independently associated with risk of stroke (odds ratio: 1.98; 95% confidence interval [CI]: 1.18–3.32; P = .009) and with the long-term cumulative incidence of stroke (hazard ratio: 2.24, 95% CI: 1.3–3.9; P = .004). In summary, we provide evidence that oxidative stress-related genetic variants, in particular, the SOD2 Val16Ala polymorphism, may represent a simple and inexpensive alternative for identifying patients at risk of stroke. |
| Databáze: | OpenAIRE |
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