Hatzlhofer Betânia L D, Bezerra Marcos André C, Santos Magnun N N, Albuquerque Dulcinéia M, Freitas Elizabete M, Costa Fernando F, Araújo Aderson S, Muniz Maria Tereza C
Centro de Hematologia e Hemoterapia de Pernambuco-HEMOPE, Recife, Pernambuco, Brasil.
Genet Test Mol Biomarkers. 2012 Sep;16(9):1038-43. doi: 10.1089/gtmb.2011.0361. Epub 2012 Aug 27.
Vaso-occlusion is a determinant for most signs and symptoms of sickle-cell anemia (SCA). The mechanisms involved in the pathogenesis of vascular complications in SCA remain unclear. It is known that genetic polymorphisms associated with thrombophilia may be potential modifiers of clinical features of SCA. The genetic polymorphisms C677T and A1298C relating to the enzyme methylenetetrahydrofolate reductase (MTHFR), a clotting Factor V Leiden mutation (1691G→A substitution of Factor V Leiden), and the mutant prothrombin 20210A allele were analyzed in this study. The aim was to find possible correlations with vascular complications and thrombophilia markers in a group of SCA patients in Pernambuco, Brazil. The study included 277 SCA patients, divided into two groups: one consisting of 177 nonconsanguineous SCA patients who presented vascular manifestations of stroke, avascular necrosis, leg ulcers, priapism, and acute chest syndrome (group 1); and the other consisting of 100 SCA patients without any reported vascular complication (group 2). Molecular tests were done using either polymerase chain reaction (PCR) restriction fragment length polymorphism or allele-specific PCR techniques. Comparisons between the groups were made using the χ(2) test. The 677 CT and TT genotypes showed a significant risk of vascular complications (p=0.015). No significant associations between the groups were found when samples were analyzed for the MTHFR A1298C allele (p=0.913), Factor V G1691 (p=0.555), or prothrombin G20210A mutation (p=1.000). The polymorphism MTHFR C677T seemed to be possibly predictive for the development of some vascular complications in SCA patients among this population.
血管闭塞是镰状细胞贫血（SCA）大多数体征和症状的决定因素。SCA血管并发症发病机制中涉及的机制仍不清楚。已知与血栓形成倾向相关的基因多态性可能是SCA临床特征的潜在调节因素。本研究分析了与亚甲基四氢叶酸还原酶（MTHFR）相关的基因多态性C677T和A1298C、凝血因子V莱顿突变（因子V莱顿的1691G→A替换）以及突变的凝血酶原20210A等位基因。目的是在巴西伯南布哥州的一组SCA患者中寻找与血管并发症和血栓形成倾向标志物的可能相关性。该研究纳入了277例SCA患者，分为两组：一组由177例非近亲SCA患者组成，他们出现了中风、无血管性坏死、腿部溃疡、阴茎异常勃起和急性胸部综合征等血管表现（第1组）；另一组由100例无任何血管并发症报告的SCA患者组成（第2组）。分子检测采用聚合酶链反应（PCR）限制性片段长度多态性或等位基因特异性PCR技术。组间比较采用χ²检验。677 CT和TT基因型显示出血管并发症的显著风险（p = 0.015）。当分析样本的MTHFR A1298C等位基因（p = 0.913）、因子V G1691（p = 0.555）或凝血酶原G20210A突变（p = 1.000）时，两组之间未发现显著关联。在该人群的SCA患者中，多态性MTHFR C677T似乎可能预测某些血管并发症的发生。
