The polymorphism of monocyte chemoattractant protein-1 is associated with the renal disease of SLE.
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.


CONCLUSIONS
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.
Kim
Hyun Lee
HL
Department of Internal Medicine, College of Medicine, Chosun University, Seoul, Korea.
Lee
Dong-Sup
DS
Yang
Seung Hee
SH
Lim
Chun Soo
CS
Chung
Jong Hoon
JH
Kim
Suhnggwon
S
Lee
Jung Sang
JS
Kim
Yo Su
YS
D024506:5' Flanking Region / Q000235:genetics; D000225:Adenine / Q000378:metabolism; D000328:Adult; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics* / Q000652:urine; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005838:Genotype; D006147:Guanine / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000209:etiology* / Q000235:genetics* / Q000652:urine; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications* / Q000235:genetics* / Q000652:urine; D008181:Lupus Nephritis / Q000097:blood / Q000652:urine; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*
D018932:Chemokine CCL2; D006147:Guanine; D000225:Adenine