Moreira Neto F, Lourenço D M, Noguti M A E, Morelli V M, Gil I C P, Beltrão A C S, Figueiredo M S
Disciplina de Hematologia e Hemoterapia, Paulista de Medicina, Universidade Federal de São Paulo, Rua Botucatu 740, 04023-900 São Paulo, SP, Brazil.
Braz J Med Biol Res. 2006 Oct;39(10):1291-5. doi: 10.1590/s0100-879x2006001000004. Epub 2006 Aug 22.
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, beta-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.
镰状细胞病（SCD）是世界上最常见的遗传性疾病之一，患者表现出显著的临床异质性。已知SCD患者存在凝血和纤溶系统的激活，尤其是在血管闭塞性危象期间，以及疾病的稳定期。我们确定了因子V基因G1691A突变（因子V莱顿突变）、凝血酶原基因G20210A变异以及亚甲基四氢叶酸还原酶（MTHFR）C677T多态性是否可能是SCD个体发生血管并发症的危险因素。我们研究了53例SCD患者（60%为女性），其中29例为SS型（镰状细胞贫血；28岁，范围：13 - 52岁），24例为SC型（镰状 - 血红蛋白C病；38.5岁，范围：17 - 72岁）血红蛋白病。通过聚合酶链反应（PCR）鉴定因子V莱顿突变、MTHFR C677T多态性和凝血酶原G20210A变异，随后用特定的内切酶进一步消化PCR产物。记录了以下血管并发症：中风、视网膜病变、急性胸综合征以及X线证实的无血管性坏死。仅1例患者为因子V莱顿突变杂合子（1.8%），且不存在凝血酶原G20210A变异。在1例患者中检测到MTHFR 677TT多态性（1.8%），在18例患者中观察到杂合形式677TC（34%，9例SS型和9例SC型疾病），其患病率与其他人报道的相似。未检测到MTHFR 677T等位基因的存在与其他基因调控因素之间的关联，如α地中海贫血、β珠蛋白基因单倍型和胎儿血红蛋白。MTHFR 677T等位基因的存在与SCD中血管并发症的发生相关，尽管在分别考虑每种并发症时这种关联并不显著。总之，MTHFR C677T多态性可能是SCD中血管并发症的一个危险因素。
