Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Exp Mol Pathol. 2022 Oct;128:104834. doi: 10.1016/j.yexmp.2022.104834. Epub 2022 Sep 22.
Sickle cell disease (SCD) is an inherited genetic disorders of hemoglobin that causes multisystem morbidity. The pathophysiology of SCD is complex and includes HbS polymerization/sickling, hemolysis, endothelial dysfunction and inflammation. Chemokines are proteins playing an important role in the inflammation process and could be involved the context of pro-inflammatory SCD. Some chemokine polymorphism were found to be associated with clinical complication in SCD.
Was to explore the frequency and the possible effect of Monocyte Chemo-attractant Protein 1-2518A/G (MCP1-2518A/G) and Chemokine Receptor 2-V64I (CCR2-V64I) genetic polymorphisms on clinical and laboratory disease-related variables in Egyptian Sickle cell disease patients.
Genotyping of the two genes were performed by PCR-RFLP technique for 80 SCD patients as well as 50 healthy control group.
The study revealed that the MCP1-2518 polymorphic genotypes (AG & GG) showed no statistically significant difference in the distribution of the polymorphic genotypes between SCD patients and the controls (p = 0.164). While a significantly higher frequency of the mutant variants CCR2-V64I GA/AA among SCD patients than the control subjects were found (p = 0.032). Regarding the clinic-pathological features, the frequency of recurrent infections, vaso-occlusive crisis, severe vaso-occlusive crisis and number of hospitalization/year were higher in patients harbouring the MCP1-2518A/G and CCR2-V64I polymorphic genotypes than the wild genotype, and gall bladder complications were higher in MCP1-2518 G allele patients, whereas surgical splenectomy were higher in CCR2-V64I A allele patients (p < 0.05).
MCP1-2518A/G and CCR2-V64I genetic polymorphisms may influence the clinical severity of sickle cell disease.
镰状细胞病（SCD）是一种遗传性血红蛋白疾病，可导致多系统发病。SCD 的病理生理学较为复杂，包括 HbS 聚合/镰变、溶血、内皮功能障碍和炎症。趋化因子在炎症过程中发挥着重要作用，可能与促炎 SCD 有关。一些趋化因子多态性与 SCD 的临床并发症有关。
探讨单核细胞趋化蛋白 1-2518A/G（MCP1-2518A/G）和趋化因子受体 2-V64I（CCR2-V64I）基因多态性在埃及 SCD 患者的临床和实验室疾病相关变量中的频率和可能的影响。
采用 PCR-RFLP 技术对 80 例 SCD 患者和 50 例健康对照组进行了这两种基因的基因分型。
研究表明，MCP1-2518 多态基因型（AG 和 GG）在 SCD 患者和对照组之间的分布无统计学意义（p=0.164）。而 SCD 患者中 CCR2-V64I 突变基因型 GA/AA 的频率明显高于对照组（p=0.032）。在临床病理特征方面，携带 MCP1-2518A/G 和 CCR2-V64I 多态基因型的患者比野生型患者更容易出现复发性感染、血管阻塞危象、严重血管阻塞危象和年住院次数增加，MCP1-2518 G 等位基因患者更容易出现胆囊并发症，而 CCR2-V64I A 等位基因患者更容易进行手术脾切除术（p<0.05）。
MCP1-2518A/G 和 CCR2-V64I 遗传多态性可能影响镰状细胞病的临床严重程度。
