The impact of MCP1-2518A/G and CCR2-V64I genetic polymorphisms in Egyptian sickle cell disease patients

Abstract

BackgroundSickle 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. Aim of the studyWas 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. Patients and methodsGenotyping of the two genes were performed by PCR-RFLP technique for 80 SCD patients as well as 50 healthy control group. ResultsThe 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). In conclusionMCP1–2518A/G and CCR2-V64I genetic polymorphisms may influence the clinical severity of sickle cell disease.