eNOS intron 4 and eNOS T>C gene polymorphisms may be used as a genetic marker of prognostic value in SCD, as they are associated with unfavorable clinical outcomes.

Sickle cell disease (SCD) is associated with a pro-inflammatory state, characterized by an elevated baseline leukocyte count and inflammatory cytokines. Inflammation, white blood cell (WBC) adhesion to vascular endothelium with subsequent endothelial injury, and repeated ischemia-reperfusion injury contribute to disease pathogenesis. Identification of genetic polymorphisms that may modulate disease severity in SCD is becoming a field of interest. The Duffy blood group antigen has been identified as a receptor for various chemokines involved in neutrophil activation and trafficking. This study aimed at investigating the effect of RBCs' Duffy antigen expression and its genetic polymorphisms on modulating disease severity and its complications among Egyptian sickle cell patients. Methods We analyzed the association of Duffy genotypes and phenotypes with clinical expression of SCD in 100 Egyptian patients. The Duffy phenotype expression was detected by indirect anti-globulin test while Duffy genotyping was conducted with polymerase chain reaction-restriction fragment length polymorphism-based assay. Results Total WBC count was strongly associated with Duffy genotype. WBCs were significantly higher in Duffy-positive patients (P = 0.002). No statistical significance was evident between individual measures of disease severity (pulmonary dysfunction, avascular necrosis, central nervous system dysfunction, kidney dysfunction, and leg ulcers) and Duffy genotype. Conclusion Our study suggests that RBC Duffy expression increases levels of WBCs in SCD patients and that Duffy genotype may not be a potential biomarker for end-organ damage in SCD.

No abstract

Background Plasminogen activator inhibitor-1 (PAI-1) is a key molecule residing at the nexus between thrombosis and inflammatory processes. Recently, PAI-1 and its gene expression have emerged as a potential candidate for autoimmune disorders such as SLE. Objective To investigate whether the PAI-1 4G/5G polymorphism at position −675 could be a genetic marker for susceptibility to childhood-onset SLE and development of lupus nephritis among Egyptian children and adolescents. Methods Three hundred fifty patients diagnosed with childhood-onset SLE and 350 well-matched healthy controls were included in this multi-center study. All subjects were genotyped for the PAI-1 promoter 4G/5G polymorphism at position −675 using PCR– restriction fragment length polymorphism (RFLP). Serum PAI-1 levels were measured by ELISA. Results The PAI-1 (- 675) 4G/4G genotype was more represented in c-SLE patients, as compared to the control group (38% vs 23%; OR =2.7; [95% CI: 1.47–2.9]; P < 0.001). Patients carrying the PAI-1 4G/4G genotype or 4G allele were more likely to develop lupus nephritis (OR: 3.38; [95% CI: 1.9–5.9]; P <0.001, for the 4G/4G genotype and OR: 2.6; [95% CI: 1.85–3.67]; for the 4G allele; P < 0.01). The PAI-1 4G/4G genotype was associated with higher PAI-1 serum concentrations (mean; 86.6±22.7 ng/mL) as compared to those with a 4G/5G genotype (mean; 48.3±16.5 ng/mL) and the lowest for the 5G/5G genotype (mean; 34.7±11.4 ng/mL); P = 0.004. Conclusion The PAI-1 4G/5G polymorphism may confer susceptibility to childhood-onset SLE and development of lupus nephritis among Egyptian children and adolescents. Moreover, the PAI-1 4G/4G genotype and 4G allele were associated with higher PAI-1 serum levels and higher disease activity scores.

Protein Z has been reported to exert an important role in inhibiting coagulation. Polymorphisms in the protein Z gene (PROZ) may affect protein Z levels and thus play a role in thrombosis. This study aimed to investigate the prevalence and clinical significance of protein Z gene G79A polymorphism in Egyptian patients with systemic lupus erythematosus (SLE). We studied the distribution of the protein Z gene (rs17882561) (G79A) single-nucleotide polymorphism by PCR-restriction fragment length polymorphism in 100 Egyptian patients with SLE and 100 age, sex, and ethnically matched controls. There was no statistically significant difference in the distribution of the genotypes between SLE patients and the control group in our study (P = 0.103). But a statistically significant difference in the frequency of the alleles between SLE patients and controls was observed (P = 0.024). Also a significant association was detected between protein Z genotypes (and also A allele) and thrombosis, which is one of the manifestations of SLE (P = 0.004 and P = 0.001, respectively). Moreover, we observed a significant association between the protein Z AA and GA genotypes (and also A allele) and the presence of anticardiolipin antibodies (P = 0.016 and P = 0.004, respectively). The minor A allele of the G79A polymorphism in the protein Z gene might contribute to the genetic susceptibility of SLE in Egyptian patients. Also, an influence for this polymorphism on some of the disease manifestations has been elucidated, so protein Z G79A AG/AA may be a risk factor for thrombosis.