Plasminogen activator inhibitor-1 gene polymorphism 4G/4G genotype and lupus nephritis in Chinese patients

Background Abnormal regulation in the coagulation and fibrinolytic system m ay play an important role in mediating glomerular damage in lupus nephritis . Indeed, glomerular thrombosis occurs frequently in lupus nephritis and pr edicts the future development of glomerular sclerosis. In the murine model of active lupus nephritis, plasminogen activator inhibitor-1 (PAI-1) gene w as overexpressed throughout the kidney, both within the glomeruli and also in tubules and vessels. The level of PAI-1 expression in the tissues appear ed to correlate with the progression of lupus nephritis. Recently, a single base pair insertion/deletion 4G/5G polymorphism of the PAI-1 gene has been identified and shown to alter plasma PAI-1 activity. This study was theref ore conducted to determine the association of the 4G/5G polymorphism of the PAI-1 gene with the development and severity of lupus nephritis. Methods. The PAI-1 gene polymorphism of 118 systemic lupus erythematosus (S LE) patients and 103 healthy controls who were gender and age matched was d etermined using standard polymerase chain reaction. PAI-1 genotype results were studied in relationship to the development and severity of lupus nephr itis. Results. Allele frequencies of 4G/5G allele were 0.59/0.41 in lupus patient s and 0.59/0.41 in controls (P = 1.000). No significant difference was note d in the genotype distribution between SLE patients with and without nephri tis. However, lupus nephritis patients with the 4G4G genotype showed signif icantly heavier proteinuria (5.0 vs. 3.7 g/day; P = 0.023) when compared wi th patients with 4G5G and 5G5G genotypes. Also, 73.3% patients with 4G4G ha d an activity index greater than or equal to8 versus 37.3% patients with 4G 5G and 5G5G (P = 0.003). Extensive necrotizing lesions were seen in 51.7% p atients with 4G4G as compared with 23.5% patients with 4G5G and 5G5G (P = 0 .014). The association of the 4G4G gene polymorphism with a higher nephriti s activity and more severe necrotizing lesions persisted when only class II I and class IV nephritis patients were studied. On the other hand, no signi ficant association was noted between the PAI-1 gene polymorphism and the ch ronicity of the nephritis. Conclusion. These findings suggest that the 4G/5G polymorphism of the PAI-I gene is associated with the activity but not the chronicity of lupus nephr itis. The presence of the 4G4G genotype does not increase the risk of devel oping SLE or lupus nephritis, but predicts the development of higher nephri tis activity and more extensive necrotizing lesions.