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

Background: 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 inflam-mation 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 study: 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.Patients and methods: Genotyping of the two genes were performed by PCR-RFLP technique for 80 SCD patients as well as 50 healthy control group.Results: 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 geno-type, 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 conclusion: MCP1-2518A/G and CCR2-V64I genetic polymorphisms may influence the clinical severity of sickle cell disease.

Automated summary

This study aimed to explore the frequency and possible effect of MCP1-2518A/G and CCR2-V64I genetic polymorphisms on clinical and laboratory variables in Egyptian Sickle cell disease patients. The study revealed that CCR2-V64I genetic polymorphism was significantly associated with SCD patients compared to the control subjects. The polymorphic genotypes were also found to influence the clinical severity of sickle cell disease.