Shaheen Iman, Khorshied Mervat, Abdel-Raouf Rasha, Gouda Heba, Kamal Dina, Abulata Nelly, Aboukhalil Reham, Meligy Basant
Departments of Clinical and Chemical Pathology.
Pediatric, Faculty of Medicine, Cairo University, Cairo, Egypt.
J Pediatr Hematol Oncol. 2020 Nov;42(8):e707-e711. doi: 10.1097/MPH.0000000000001839.
Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy characterized by increased cellular adhesiveness. Vaso-occlusion (VOC) is the most prevalent disease complication of SCD that could be altered by genetic factors. L-Selectin and integrin alpha 2 (ITGA2) are 2 adhesion molecules linked to vasculopathy and inflammation. The current study aimed at detecting the prevalence of genetic variants of L-selectin and ITGA2 as possible molecular modulators and novel therapeutic targets in a cohort of pediatric SCD patients. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism technique for 100 SCD patients and 100 age and gender-matched unrelated healthy controls. The homomutant genotype of ITGA2 C807T was significantly higher in SCD patients compared with controls (P=0.001) and confirmed almost a 3-fold increased risk of moderate and severe attacks of VOC. There are significant adverse effects caused by the polymorphisms of ITGA2, and hence Egyptian SCD patients could benefit from the targeted therapies specifically against ITGA2 to ameliorate the severe course of the disease and improve the quality of life. However, further studies of genotypes and expression levels of these adhesion molecules during the attacks of VOC are recommended.
镰状细胞病（SCD）是一种常染色体隐性血红蛋白病，其特征是细胞黏附性增加。血管闭塞（VOC）是SCD最常见的疾病并发症，可能受遗传因素影响。L-选择素和整合素α2（ITGA2）是与血管病变和炎症相关的两种黏附分子。本研究旨在检测L-选择素和ITGA2基因变异的发生率，这些变异可能是儿科SCD患者群体中的分子调节因子和新的治疗靶点。采用聚合酶链反应-限制性片段长度多态性技术对100例SCD患者以及100例年龄和性别匹配的无血缘关系健康对照进行基因分型。与对照组相比，SCD患者中ITGA2 C807T的纯合突变基因型显著更高（P = 0.001），并且证实中度和重度VOC发作风险几乎增加了3倍。ITGA2的多态性会导致显著的不良影响，因此埃及SCD患者可能会从针对ITGA2的靶向治疗中受益，以改善疾病的严重病程并提高生活质量。然而，建议进一步研究这些黏附分子在VOC发作期间的基因型和表达水平。
