Genetic polymorphisms and cerebrovascular disease in children with sickle cell anemia from Rio de Janeiro, Brazil

Filho, Isaac Lima da Silva; Leite, Ana Cláudia Celestino Bezerra; Moura, Paulo; Ribeiro, Georgina Severo; Cavalcante, Andréa Cony; Azevedo, Flávia Carolina Marques de; Andrada-Serpa, Maria José

doi:10.1590/s0004-282x2011000400004

Cited by 23 publications

(16 citation statements)

References 29 publications

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“…4,12 Furthermore, the effects of α-thalassemia on cerebral vasculopathy and stroke risk in SCA have been mixed with some studies showing a protective benefit 13–18 while others have not. 10,19–21 In the University of Ibadan cohort of SCA patients, α-thalassemia was commonly observed but was not associated with a statistically significant reduction in the frequency of SCA-related complications.…”

Section: Discussionmentioning

confidence: 99%

Associations of α-thalassemia and BCL11A with stroke in Nigerian, United States, and United Kingdom sickle cell anemia cohorts

et al. 2017

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Alpha-thalassemia and the BCL11A rs1427407 T allele are commonly observed in sickle cell anemia (SCA) patients and are associated with reduced hemolysis and higher hemoglobin F levels, respectively. We investigated whether a high-risk genetic profile, defined as SCA patients who did not inherit either α-thalassemia or the BCL11A rs1427407 T allele, had stronger associations with clinical and laboratory variables than the individual genetic components in the University of Ibadan cohort (n=249). We then replicated our findings in SCA cohorts from the University of Illinois at Chicago (UIC)(n=260) and Walk-Treatment of Pulmonary Hypertension and Sickle cell disease with Sildenafil Therapy (Walk-PHaSST)(n=387). High-risk was associated with higher reticulocytes (15.0% vs. 7.8%, P=0.08) and stroke history (6% vs. 1%, P=0.02) than standard risk patients and these associations were more significant than the individual genetic components in the University of Ibadan cohort. These findings were replicated in high-risk patients from UIC and Walk-PHaSST for reticulocytes (UIC: 13.5% vs. 11.8%, P=0.03; Walk-PHaSST: 9.6% vs. 8.2%, P=0.0003) and stroke history (UIC: 32% vs. 22%, P=0.07; Walk-PHaSST: 14% vs. 7%, P=0.01). On combined analysis, high-risk had strong associations with increased markers of hemolysis (hemoglobin β= −0.29, 95%CI: −0.50 to −0.09; P=0.006; reticulocyte% β=2.29, 95%CI: 1.31 to 3.25; P=1x10−5) and stroke history (OR=2.0, 95%CI: 1.3 to 3.0; P=0.0002), but no association with frequent vaso-occlusive crises (≥3/year). A high-risk genetic profile is associated with increased hemolysis and stroke history in three independent cohorts. This profile may help identify patients to prioritize for hydroxyurea and for closer monitoring strategies for stroke.

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Section: Discussionmentioning

confidence: 99%

Associations of α-thalassemia and BCL11A with stroke in Nigerian, United States, and United Kingdom sickle cell anemia cohorts

et al. 2017

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“…Brazilian studies also found a correlation between SCA clinical manifestations, Hb Fand the beta S-globin haplotype ( 8 , 9 , 13 , 19 , 25 , 29 , 30 ) , including more vaso-occlusive crises ( 9 , 29 ) , more infections ( 9 ) and slower growth ( 29 ) in the CAR haplotype, high levels of Hb F ( 13 , 19 , 25 ) and nitrites in the BEN haplotype ( 19 ) , and increased risk of cerebro vascular disease (CVD) in children with the Bantu/atypical haplotype compared to other beta S-globin haplotypes ( 30 ) . Patients with the CAR/BEN haplotype had less painful crises compared to the other haplotypes ( 22 ) .…”

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confidence: 82%

Sickle cell anemia: clinical diversity and beta S-globin haplotypes

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Revista Brasileira De Hematologia E Hemoterapia

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“…HBA (α‐globin gene) deletion has been associated with normal TCD measurement and with the absence of vasculopathy on MRA images in patients with SCA, suggesting that α‐thalassaemia may play a protective role against cerebral vasculopathy (Hsu et al , ; Bernaudin et al , ; Belisario et al , ). However, in a small case control study, HBA deletion was found not to be significantly associated with reduced risk for specific neurological events (transient ischaemic attacks, ischaemic strokes or haemorrhagic strokes) (Filho et al , ). Taken together, studies evaluating the association between either G6PD or HBA status on cerebral vasculopathy have had mixed results, possibly due in part to the small sample size and in some cases the inherent biases associated with single institution studies.…”

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confidence: 99%

Magnetic resonance angiography‐defined intracranial vasculopathy is associated with silent cerebral infarcts and glucose‐6‐phosphate dehydrogenase mutation in children with sickle cell anaemia

et al. 2012

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Summary Silent cerebral infarct (SCI) is the most commonly recognized cause of neurological injury in sickle cell anaemia (SCA). We tested the hypothesis that magnetic resonance angiography (MRA)-defined vasculopathy is associated with SCI. Furthermore, we examined genetic variations in glucose-6-phosphate dehydrogenase (G6PD) and HBA (α-globin) genes to determine their association with intracranial vasculopathy in children with SCA. Magnetic resonance imaging (MRI) of the brain and MRA of the cerebral vasculature were available in 516 paediatric patients with SCA, enrolled in the Silent Infarct Transfusion (SIT) Trial. All patients were screened for G6PD mutations and HBA deletions. SCI were present in 41.5%(214 of 516) of SIT Trial children. The frequency of intracranial vasculopathy with and without SCI was 15.9% and 6.3%, respectively (p<0.001). Using a multivariate logistic regression model, only the presence of a SCI was associated with increased odds of vasculopathy (p=0.0007, odds ratio (OR) 2.84; 95% Confidence Interval (CI)=1.55-5.21). Among male patients with SCA, G6PD status was associated with vasculopathy (p=0.04, OR 2.78; 95% CI=1.04-7.42), while no significant association was noted for HBA deletions. Intracranial vasculopathy was observed in a minority of children with SCA, and when present, was associated with G6PD status in males and SCI.

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Genetic polymorphisms and cerebrovascular disease in children with sickle cell anemia from Rio de Janeiro, Brazil

Cited by 23 publications

References 29 publications

Associations of α-thalassemia and BCL11A with stroke in Nigerian, United States, and United Kingdom sickle cell anemia cohorts

Associations of α-thalassemia and BCL11A with stroke in Nigerian, United States, and United Kingdom sickle cell anemia cohorts

Sickle cell anemia: clinical diversity and beta S-globin haplotypes

Magnetic resonance angiography‐defined intracranial vasculopathy is associated with silent cerebral infarcts and glucose‐6‐phosphate dehydrogenase mutation in children with sickle cell anaemia

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