Belhaj Nefissi Rim, Doggui Radhouene, Ouali Faida, Messaoud Taieb, Gritli Nasreddine
a Laboratory of Molecular Biology, Department of Hematology , Military Hospital of Tunis , Tunisia.
b Laboratory of Biochemistry and Molecular Biology , Children's Hospital of Tunis , Tunisia.
Hemoglobin. 2018 Mar;42(2):96-102. doi: 10.1080/03630269.2018.1451340.
Sickle cell disease is a genetic disorder characterized by a hypercoagulable state. Several complications in this hemoglobinopathy are increased by thrombosis. Factor V Leiden (FVL), prothrombin (PRT) G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C mutations are major inherited risk factors of thrombotic complications. In this study, our aim was to compare the frequencies of these mutations in sickle cell patients with healthy controls. The study population comprised 35 homozygous Hb S (HBB: c.20A>T) patients, 29 compound heterozygous patients [16 Hb S/β-thalassemia (β-thal), four Hb S/β-thal, seven Hb S/Hb C (HBB: c.19G>A) and two Hb S/Hb O-Arab (HBB: c.364G>A)] and 100 healthy subjects. All patients and controls were subjected to laboratory investigations as well as mutation genotyping. Our findings showed a severe anemia with the lowest values of protein S (PS), protein C (PC) and antithrombin (AT) in the homozygous Hb S group compared to Hb S/Hb C and Hb S/β-thal subjects. No significant difference in FVL genotype between patients and controls was observed, whereas high frequencies of PRT G20210A, MTHFR C677T and MTHFR A1298C mutations in the Hb S patients and a significant association between the MTHFR C677T mutation and Hb S/β-thal were found.
镰状细胞病是一种以高凝状态为特征的遗传性疾病。这种血红蛋白病的几种并发症会因血栓形成而增加。因子V莱顿（FVL）、凝血酶原（PRT）G20210A以及亚甲基四氢叶酸还原酶（MTHFR）C677T和A1298C突变是血栓形成并发症的主要遗传风险因素。在本研究中，我们的目的是比较镰状细胞病患者与健康对照人群中这些突变的频率。研究人群包括35名纯合子Hb S（HBB：c.20A>T）患者、29名复合杂合子患者[16名Hb S/β地中海贫血（β-地贫）、4名Hb S/β地贫、7名Hb S/Hb C（HBB：c.19G>A）和2名Hb S/Hb O-阿拉伯型（HBB：c.364G>A）]以及100名健康受试者。所有患者和对照均接受了实验室检查以及突变基因分型。我们的研究结果显示，与Hb S/Hb C和Hb S/β地贫受试者相比，纯合子Hb S组存在严重贫血，且蛋白S（PS）、蛋白C（PC）和抗凝血酶（AT）水平最低。患者与对照之间FVL基因型未观察到显著差异，然而，在Hb S患者中发现PRT G20210A、MTHFR C677T和MTHFR A1298C突变的频率较高，并且发现MTHFR C677T突变与Hb S/β地贫之间存在显著关联。
