title: Strong association of a functional polymorphism in the monocyte chemoattractant protein 1 promoter gene with lupus nephritis.
abstract: OBJECTIVE
  Lupus nephritis (LN) is a major contributor to morbidity and mortality in patients with systemic lupus erythematosus (SLE). There is evidence that polymorphisms in the genes of inflammatory mediators may predispose to the development of LN in patients with SLE. In this study, we examined the role of a functional monocyte chemoattractant protein 1 (MCP-1) polymorphism in SLE and LN.
  
  
  METHODS
  DNA and paired urine and serum samples were obtained from 134 SLE patients (> or =4 American College of Rheumatology criteria for SLE; 49 with and 85 without LN) and 118 controls. MCP-1 genomic variants were detected by polymerase chain reaction followed by restriction enzyme-fragment analysis. Urinary and serum MCP-1 levels and MCP-1 production by peripheral blood macrophages were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The A/A genotype was more common in controls than in SLE patients (P = 0.0002), whereas both the A/G (P = 0.009) and G/G (P = 0.0212) genotypes were more frequent in SLE patients. The A/A genotype was observed in only 23% of the patients with LN compared with 58% of those without LN (P < 0.0001). MCP-1 production by peripheral blood mononuclear cells from patients with the A/G and G/G phenotypes was markedly higher than the production by cells from patients with the A/A genotype. Urinary levels of MCP-1 were significantly higher in patients with LN.
  
  
  CONCLUSIONS
  These results suggest that an A/G or G/G genotype may predispose to the development of SLE and further indicate that SLE patients with these genotypes may be at higher risk of developing LN. Moreover, measurement of urinary levels of MCP-1 may be a useful tool for the detection and management of LN.
authors.affiliation: University of Florida, and Malcom Randall VA Medical Center, Gainesville, 32610, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Tucci
authors.forename: Elena V
authors.initials: EV
authors.lastname: Barnes
authors.forename: Eric S
authors.initials: ES
authors.lastname: Sobel
authors.forename: Byron P
authors.initials: BP
authors.lastname: Croker
authors.forename: Mark S
authors.initials: MS
authors.lastname: Segal
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
authors.forename: Hanno B
authors.initials: HB
authors.lastname: Richards
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics* / Q000652:urine; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000502:physiology; D008181:Lupus Nephritis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D015533:Transcriptional Activation
chemical_list: D018932:Chemokine CCL2