Abstract
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 (sickle-hemoglobin 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 alpha-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.
Highlights
Sickle cell disease (SCD) is one of the most common inherited diseases in the world
We investigated the hypothesis that the presence of the factor V gene G1691A mutation, the prothrombin gene G20210A variant, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may be a risk factor for vascular complications in individuals with SS and SCD
Median hemoglobin level was lower for SS patients (7.95 g/dL) than for SC patients (11.53 g/ dL), whereas fetal hemoglobin level was higher for SS patients (6.2%) than for SC patients (2.1%)
Summary
Sickle cell disease (SCD) is one of the most common inherited diseases in the world. In Brazil, 700 to 1000 infants with SCD are estimated to be born each year [1]. Even with the same inherited DNA mutation within the ß-globin gene, patients present a notorious clinical heterogeneity. Additional genetic factors such as α-thalassemia, fetal hemoglobin synthesis, and ß-globin haplotype have been identified, but none of these can fully explain the differences in clinical expression observed in these patients. There are other elements that contribute to the many phenotypes of the disease [2,3,4,5] It has been known for a long time that patients with SCD show activation of the blood coagulation and fibrinolytic systems, as well as increased platelet activity and consumption of coagulation inhibitors, especially during vaso-occlusive crises, and during the steady state of the disease [69]. Because of the importance of vascular complications in the pathophysiology of SCD, a number of genetic polymorphisms associated with thrombophilia have been studied as potential genetic modifiers of SCD
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More From: Brazilian Journal of Medical and Biological Research
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