Association of Plasminogen Activator Inhibitor 1 (PAI-1) 4G/5G Polymorphism and Susceptibility to SLE in Egyptian
Aly A Yousef1, Faisal Y Mohamed2, Naglaa F Boraey3
1Department of Pediatrics, Faculty of Medicine, Helwan University, Helwan, Egypt.
Insights
The Plasminogen activator inhibitor-1 (PAI-1) 4G/4G genotype is linked to increased childhood-onset SLE susceptibility and lupus nephritis in Egyptian children. This genotype also correlates with higher PAI-1 serum levels.
Area of Science:
- Genetics
- Immunology
- Pediatrics
Background:
- Plasminogen activator inhibitor-1 (PAI-1) is implicated in thrombosis and inflammation.
- PAI-1 gene expression is a potential factor in autoimmune disorders like Systemic Lupus Erythematosus (SLE).
- Childhood-onset SLE (c-SLE) and lupus nephritis are significant health concerns in pediatric populations.
Purpose of the Study:
- To determine if the PAI-1 4G/5G polymorphism at position -675 acts as a genetic marker for c-SLE.
- To assess the association between this polymorphism and the development of lupus nephritis in Egyptian children.
- To investigate the correlation between PAI-1 genotype, serum PAI-1 levels, and disease activity.
Main Methods:
- A multi-center study involving 350 Egyptian children with c-SLE and 350 healthy controls.
- Genotyping for the PAI-1 promoter 4G/5G polymorphism using PCR-RFLP.
- Quantification of serum PAI-1 levels via ELISA.
Main Results:
- The PAI-1 4G/4G genotype was significantly more prevalent in c-SLE patients (38%) compared to controls (23%).
- Carrying the PAI-1 4G/4G genotype or 4G allele increased the likelihood of developing lupus nephritis.
- The PAI-1 4G/4G genotype was associated with significantly higher serum PAI-1 concentrations compared to 4G/5G and 5G/5G genotypes.
Conclusions:
- The PAI-1 4G/5G polymorphism may predispose Egyptian children to c-SLE and lupus nephritis.
- The PAI-1 4G/4G genotype and 4G allele are linked to elevated PAI-1 serum levels.
- Higher disease activity scores were observed in patients with the PAI-1 4G/4G genotype.
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.
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