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.