Association of PON1 gene polymorphisms, paraoxonase 1 gene expression and activity in Egyptian children and adolescents with sickle cell disease

Sickle cell disease (SCD) is defined by chronic oxidative stress, hemolysis, vaso-occlusive crisis (VOC), endothelial injury, and end-organ damage. Paraoxonase1 (PON-1) serves a significant function as an anti-inflammatory and antioxidant agent. This study investigates PON1c.55L > M and PON1c.192Q > R polymorphism frequency in Egyptian children and adolescents with SCD, as well as the impact of these polymorphisms on PON-1 gene expression and enzymatic activity. The study recruited 70 SCD children in addition to 70 healthy matched participants as controls. Laboratory parameters, PON-1 gene molecular analysis, PON-1 gene expression, and enzymatic activity were investigated. PON-1 activity and expression were substantially reduced in patients with SCD than in controls (P < 0.001). We detected higher allelic frequencies of PON1c.192R (52.9% in SCD cases and 25.7% in controls). For PON1c.192Q > R, compared with the genotype QQ, we found genotype QR, and RR were significantly associated with increased SCD risk. Alternatively, the PON1c.55L > M variant allele had no significant association with SCD risk. Furthermore, SCD cases with the homozygote variant PON1c.192 RR, PON1c.55 MM genotypes exhibited decreased PON1 activity relative to controls possessing corresponding genotypes. SCD patients with the RR genotype in SCD exhibited notable reductions in RBC count, MCH, and MCHC, alongside substantial rises in WBCs, neutrophil count, LDH, ferritin, creatinine, cystatin C, and BUN levels. Additionally, substantial correlations were identified between the MM genotype variant and decreased RBC counts, alongside a notable increase in WBC count, serum ferritin, and cystatin C levels. A positive correlation between PON-1 activity and hematocrit (r = 0.26; P < 0.05) was identified in patients with SCD. Conversely, negative correlations were found with WBCs (r = -0.47; P < 0.001), creatinine (r = − 29; P < 0.05), cystatin C (r = − 37; P < 0.001) and ferritin levels (r = − 0.34; P < 0.05). The PON1c.55L > M and PON 1c.192Q > R gene polymorphisms in SCD cases influenced the PON-1 gene expression and activity. SCD cases with the variant PON1c.192 RR, PON1c.55 LL and MM genotypes exhibited downregulated PON1 activity. This reduction was correlated with elevated hemolysis and inflammation markers, ferritin levels, creatinine, cystatin C, and BUN levels, indicating a potential link between decreased PON1 activity and renal and cardiovascular dysfunction incidence.