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

Igor F. Domingos; Diego A. Pereira-Martins; Rayssa L. Borges-Medeiros; Diego A. Falcao; Betania L. Hatzlhofer; John N. Brewin; Kate Gardner; Taciana F. Mendonca; Maria S. Cavalcanti; Anderson F. Cunha; Ana C. Anjos; Evandra S. Rodrigues; Simone Kashima; Pedro R. Cruz; Monica B. Melo; Stephan Menzel; Aderson S. Araujo; Fernando F. Costa; Marcos A. Bezerra; Antonio R. Lucena-Araujo

doi:10.1016/j.jns.2020.116839

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

Igor F. Domingos, Diego A. Pereira-Martins, Rayssa L. Borges-Medeiros, Diego A. Falcao, Betania L. Hatzlhofer, John N. Brewin, Kate Gardner, Taciana F. Mendonca, Maria S. Cavalcanti, Anderson F. Cunha, Ana C. Anjos, Evandra S. Rodrigues, Simone Kashima, Pedro R. Cruz, Monica B. Melo, Stephan Menzel, Aderson S. Araujo, Fernando F. Costa, Marcos A. Bezerra, Antonio R. Lucena-Araujo^*

^*Corresponding author for this work

Comprehensive Cancer Centre

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

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.

Original language	English
Article number	116839
Journal	Journal of the Neurological Sciences
Volume	414
DOIs	https://doi.org/10.1016/j.jns.2020.116839
Publication status	Published - 15 Jul 2020

Keywords

Adulthood
Risk factors
Sickle cell anemia
Stroke

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.jns.2020.116839

Cite this

Domingos, I. F., Pereira-Martins, D. A., Borges-Medeiros, R. L., Falcao, D. A., Hatzlhofer, B. L., Brewin, J. N., Gardner, K., Mendonca, T. F., Cavalcanti, M. S., Cunha, A. F., Anjos, A. C., Rodrigues, E. S., Kashima, S., Cruz, P. R., Melo, M. B., Menzel, S., Araujo, A. S., Costa, F. F., Bezerra, M. A., & Lucena-Araujo, A. R. (2020). Evaluation of oxidative stress-related genetic variants for predicting stroke in patients with sickle cell anemia. Journal of the Neurological Sciences, 414, Article 116839. https://doi.org/10.1016/j.jns.2020.116839

@article{e797c1619a3540359a2455e31e82a9e4,

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

abstract = "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.",

keywords = "Adulthood, Risk factors, Sickle cell anemia, Stroke",

author = "Domingos, {Igor F.} and Pereira-Martins, {Diego A.} and Borges-Medeiros, {Rayssa L.} and Falcao, {Diego A.} and Hatzlhofer, {Betania L.} and Brewin, {John N.} and Kate Gardner and Mendonca, {Taciana F.} and Cavalcanti, {Maria S.} and Cunha, {Anderson F.} and Anjos, {Ana C.} and Rodrigues, {Evandra S.} and Simone Kashima and Cruz, {Pedro R.} and Melo, {Monica B.} and Stephan Menzel and Araujo, {Aderson S.} and Costa, {Fernando F.} and Bezerra, {Marcos A.} and Lucena-Araujo, {Antonio R.}",

year = "2020",

month = jul,

day = "15",

doi = "10.1016/j.jns.2020.116839",

language = "English",

volume = "414",

journal = "Journal of the Neurological Sciences",

issn = "0022-510X",

publisher = "Elsevier B.V.",

}

Domingos, IF, Pereira-Martins, DA, Borges-Medeiros, RL, Falcao, DA, Hatzlhofer, BL, Brewin, JN , Gardner, K, Mendonca, TF, Cavalcanti, MS, Cunha, AF, Anjos, AC, Rodrigues, ES, Kashima, S, Cruz, PR, Melo, MB, Menzel, S, Araujo, AS, Costa, FF, Bezerra, MA & Lucena-Araujo, AR 2020, 'Evaluation of oxidative stress-related genetic variants for predicting stroke in patients with sickle cell anemia', Journal of the Neurological Sciences, vol. 414, 116839. https://doi.org/10.1016/j.jns.2020.116839

TY - JOUR

T1 - Evaluation of oxidative stress-related genetic variants for predicting stroke in patients with sickle cell anemia

AU - Domingos, Igor F.

AU - Pereira-Martins, Diego A.

AU - Borges-Medeiros, Rayssa L.

AU - Falcao, Diego A.

AU - Hatzlhofer, Betania L.

AU - Brewin, John N.

AU - Gardner, Kate

AU - Mendonca, Taciana F.

AU - Cavalcanti, Maria S.

AU - Cunha, Anderson F.

AU - Anjos, Ana C.

AU - Rodrigues, Evandra S.

AU - Kashima, Simone

AU - Cruz, Pedro R.

AU - Melo, Monica B.

AU - Menzel, Stephan

AU - Araujo, Aderson S.

AU - Costa, Fernando F.

AU - Bezerra, Marcos A.

AU - Lucena-Araujo, Antonio R.

PY - 2020/7/15

Y1 - 2020/7/15

N2 - 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.

AB - 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.

KW - Adulthood

KW - Risk factors

KW - Sickle cell anemia

KW - Stroke

UR - http://www.scopus.com/inward/record.url?scp=85083792158&partnerID=8YFLogxK

U2 - 10.1016/j.jns.2020.116839

DO - 10.1016/j.jns.2020.116839

M3 - Article

C2 - 32344219

AN - SCOPUS:85083792158

SN - 0022-510X

VL - 414

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

M1 - 116839

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this