Stroke is a serious complication of sickle cell anemia (SCA) affecting children and adults. Recent reports suggested that tumor necrosis factor-α (TNF-α) (–308) polymorphism is an important risk factor for stroke in children with SCA. The role of TNF-α polymorphism in the frequency of brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) abnormalities in adults with SCA is still uncertain. Our objective was to evaluate the frequency of TNF-α polymorphism in adults with SCA and to correlate it to brain MRI and MRA findings. TNF-α (–308) polymorphism was determined in 49 adults with SCA. All subjects were evaluated with brain MRI/MRA to establish the presence of intracranial abnormalities. Thirty-three (67.3%) had abnormal brain MRA scans, 8 (16.3%) had intracranial stenosis and 29 (59.2%) showed arterial tortuosity. Forty-one (83.7%) had the GG genotype and 8 had the GA genotype. There was no correlation between homozygosity for G allele and MRA or MRI abnormalities. Although TNF-α (–308) polymorphism is a potential predictor of the genetic risk for stroke in children, we found no association between the polymorphism and large vessel abnormalities in adults with SCA.

Sickle cell disease (SCD) is one of the most common inherited diseases in the world and the patients present notorious clinical heterogeneity. It is known that patients with SCD present activation of the blood coagulation and fibrinolytic systems, especially during vaso-occlusive crises, but also during the steady state of the disease. We determined if the presence of the factor V gene G1691A mutation (factor V Leiden), the prothrombin gene G20210A variant, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may be risk factors for vascular complications in individuals with SCD. We studied 53 patients with SCD (60% being women), 29 with SS (sickle cell anemia; 28 years, range: 13-52 years) and 24 with SC (sicklehemoglobin C disease; 38.5 years, range: 17-72 years) hemoglobinopathy. Factor V Leiden, MTHFR C677T polymorphism, and prothrombin G20210A variant were identified by PCR followed by further digestion of the PCR product with specific endonucleases. The following vascular complications were recorded: stroke, retinopathy, acute thoracic syndrome, and X-ray-documented avascular necrosis. Only one patient was heterozygous for factor V Leiden (1.8%) and there was no prothrombin G20210A variant. MTHFR 677TT polymorphism was detected in 1 patient (1.8%) and the heterozygous form 677TC was observed in 18 patients (34%, 9 with SS and 9 with SC disease), a prevalence similar to that reported by others. No association was detected between the presence of the MTHFR 677T allele and other genetic modulation factors, such as α-thalassemia, ß-globin gene haplotype and fetal hemoglobin. The presence of the MTHFR 677T allele was associated with the occurrence of vascular complications in SCD, although this association was not significant when each complication was considered separately. In conclusion, MTHFR C677T polymorphism might be a risk factor for vascular complications in SCD.

Sickle cell disease (SCD) is one of the most common inherited diseases in the world and the patients present notorious clinical heterogeneity. It is known that patients with SCD present activation of the blood coagulation and fibrinolytic systems, especially during vaso-occlusive crises, but also during the steady state of the disease. We determined if the presence of the factor V gene G1691A mutation (factor V Leiden), the prothrombin gene G20210A variant, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may be risk factors for vascular complications in individuals with SCD. We studied 53 patients with SCD (60% being women), 29 with SS (sickle cell anemia; 28 years, range: 13-52 years) and 24 with SC (sicklehemoglobin C disease; 38.5 years, range: 17-72 years) hemoglobinopathy. Factor V Leiden, MTHFR C677T polymorphism, and prothrombin G20210A variant were identified by PCR followed by further digestion of the PCR product with specific endonucleases. The following vascular complications were recorded: stroke, retinopathy, acute thoracic syndrome, and X-ray-documented avascular necrosis. Only one patient was heterozygous for factor V Leiden (1.8%) and there was no prothrombin G20210A variant. MTHFR 677TT polymorphism was detected in 1 patient (1.8%) and the heterozygous form 677TC was observed in 18 patients (34%, 9 with SS and 9 with SC disease), a prevalence similar to that reported by others. No association was detected between the presence of the MTHFR 677T allele and other genetic modulation factors, such as α-thalassemia, ß-globin gene haplotype and fetal hemoglobin. The presence of the MTHFR 677T allele was associated with the occurrence of vascular complications in SCD, although this association was not significant when each complication was considered separately. In conclusion, MTHFR C677T polymorphism might be a risk factor for vascular complications in SCD.

Purpose: Stroke is a common and serious complication of sickle cell disease (SCD) affecting children as well as adults. Recent reports suggested that promoter region polymorphism in the tumour necrosis factor alpha (TNF-α) gene at position −308 is an important risk factor for large vessel stroke in children with SCD. The role of TNF-α polymorphism in the frequency of magnetic resonance angiography (MRA) abnormalities in adults with SCD is still uncertain. Our objective was to evaluate TNF-α polymorphism in adults with SCD from a tertiary University-based hospital in Sao Paulo, Brazil and correlate them to brain magnetic resonance imaging (MRI) and MRA findings. Casuistic and Methods: The determination of the G-308A polymorphism of the TNF-α gene was performed in forty-nine adult patients with SCD followed in our outpatient clinic. All subjects were evaluated with brain MRI and MRA to determine the presence of previous stroke, arterial tortuosity and intracranial stenosis Results: Thirty-three patients (67.3%) had abnormal brain MRA scans (intracranial stenosis or arterial tortuosity). Eight patients (16.3%) had intracranial stenosis on MRA and 29 (59.2%) showed arterial tortuosity. Forty one patients (83.7%) had the GG TNF-α (−308) genotype and eight had the GA genotype. There were no cases of AA genotype. There was no correlation between homozygosis for the TNF-α (−308) G allele and MRA abnormalities. Conclusion: Although TNF-α (−308) polymorphism has been considered a potential predictor of genetic risk for stroke in children with SCA, we found no association between the polymorphism and large vessel abnormalities in adults with sickle cell disease. (FAPESP: 04/04498-4)