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 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 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 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 CONCLUSION: MCP1-2518A/G and CCR2-V64I genetic polymorphisms may influence the clinical severity of sickle cell disease.

Prevalence and risk factors of cognitive impairment in children with sickle cell disease in Egypt.

Little is known about cognitive impairment in patients with sickle cell disease in Africa. This study aimed to assess cognitive impairment and identify possible risk factors in patients with sickle cell disease in Egypt. This study was conducted at Cairo University Children Hospital. Patients with sickle cell disease, between ages of 6-20 years were enrolled. Cognitive ability was tested using the Stanford Binet intelligence quotient (IQ) test, fourth edition. Transcranial Doppler, magnetic resonance imaging and magnetic resonance angiography of the brain were performed within a week of the IQ test. Among the 40 enrolled patients, 55% had a Full Scale IQ at least 1 standard deviation below the mean, and 27.5% had an IQ 2 standard deviations below the mean. High lactate dehydrogenase was significantly associated with low IQ (p = 0.004). In univariate analyses, IQ was significantly correlated with older age (p = 0.025), high lactate dehydrogenase (p = 0.008) and older age at the start of hydroxyurea (p = 0.025). Impaired cognition is prevalent among sickle cell disease patients. Early initiation of hydroxyurea therapy, which should also reduce hemolysis and lactate dehydrogenase, may be a simple measure to preserve mental abilities in these patients.