Background: Renal involvement in patients with systemic lupus erythematosus (SLE) varies from none to full-blown disease. Monocyte chemoattractant protein (MCP-1) is implicated in the activation of inflammatory cells and has been suggested to affect the progression of lupus nephritis (LN).
Methods: In the 5' flanking region of the MCP-1 gene, a guanine (G)/adenine (A) transition identified at position -2518 upstream from the transcription site was reported to be associated with circulating levels. We investigated whether the G/A polymorphism was associated with clinical manifestations of SLE in terms of renal involvement and the biological significance of this polymorphism.
Results: Frequencies of MCP-1/-2518 polymorphisms were similar in patients and controls. Serum MCP-1 levels in patients with SLE were significantly greater than those of healthy controls, but amount of proteinuria did not correlate with serum MCP-1 level in patients. In AA homozygotes, patients with LN showed greater serum MCP-1 levels than patients without LN. In addition, urinary excretion of MCP-1 was greater in AA homozygotes compared with other genotypes in patients with LN. A positive correlation between urinary excretion of MCP-1 and proteinuria was observed in patients with SLE. Genetic constructs containing G at this site showed that G construct had lower activity (39%) than that shown by a construct containing A, and this response, which depended on MCP-1 genotype, was maintained after stimulation with tumor necrosis factor-alpha.
Conclusion: These results suggest that a genetic polymorphism in the 5' flanking region of the MCP-1 gene would be associated with nephritis in lupus through modulating MCP-1 expression.
Copyright 2002 by the National Kidney Foundation, Inc.