Regional Medical Research Centre for Tribals (ICMR), Jabalpur, Madhya Pradesh, India.
Eur J Haematol. 2013 Nov;91(5):462-6. doi: 10.1111/ejh.12190. Epub 2013 Sep 16.
It is known that patients with sickle cell disease (SCD) present activation of the blood coagulation and fibrinolytic systems, especially during vaso-occlusive crises and also during the steady state of the disease. We determined whether the presence of the factor prothrombin gene G20210A variant, factor V gene G1691A mutation (factor V Leiden), and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms may be risk factors for vascular complications in individuals with SCD.
The study involved 150 patients with sickle cell anemia and 150 healthy controls of Central India. Genotyping of three thrombophilic mutations was carried out by PCR-RFLP methods using MnlI, Hind III, and Hinf I, respectively, for factor V Leiden, prothrombin, and MTHFR mutations.
Patients with SCD had significantly higher prevalence of mutant variants of MTHFR gene (28.0% heterozygotes and 14.6% homozygotes) and FVL gene (14.6% heterozygotes) as compared to normal/control individuals, but complete absence of mutant variants of prothrombin gene. The patients with SCD having mutant variants of MTHFR and FVL genes showed higher incidence of pain in chest, abdomen, and bone joints along with early age of onset of clinical manifestations as well as frequent dependence on blood transfusion than those patients with SCD having wild variants of these thrombotic genes. As compared to control subjects, SCD individuals having mutant variants of FVL and MTHFR genes had significant association with higher levels of prothrombin fragment (F1+2), D-dimer, thrombin-antithrombin (TAT), and lower level of protein C.
MTHFR C677T and FVL G1691A polymorphisms may be risk factors for increased vascular complications in patient with SCD.
已知镰状细胞病（SCD）患者存在血液凝固和纤维蛋白溶解系统的激活，尤其是在血管阻塞性危象期间，以及在疾病的稳定状态期间。我们确定凝血酶原基因 G20210A 变体、因子 V 基因 G1691A 突变（因子 V 莱顿）和亚甲基四氢叶酸还原酶（MTHFR）C677T 多态性的存在是否可能是 SCD 个体血管并发症的危险因素。
这项研究涉及印度中部的 150 名镰状细胞贫血患者和 150 名健康对照者。使用 MnlI、Hind III 和 Hinf I 分别通过 PCR-RFLP 方法对三种血栓形成突变进行基因分型，用于因子 V 莱顿、凝血酶原和 MTHFR 突变。
与正常/对照个体相比，SCD 患者的 MTHFR 基因（28.0%杂合子和 14.6%纯合子）和 FVL 基因（14.6%杂合子）的突变变体的患病率显著更高，但凝血酶原基因的突变变体完全不存在。与 SCD 患者具有野生型血栓形成基因的患者相比，具有 MTHFR 和 FVL 基因突变变体的 SCD 患者具有更高的胸痛、腹痛和骨关节疼痛发生率，以及更早的临床表现发病年龄和更频繁的依赖输血。与对照组相比，具有 FVL 和 MTHFR 基因突变变体的 SCD 个体与较高水平的凝血酶原片段（F1+2）、D-二聚体、凝血酶-抗凝血酶（TAT）和较低水平的蛋白 C 显著相关。
MTHFR C677T 和 FVL G1691A 多态性可能是 SCD 患者血管并发症增加的危险因素。
