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 (>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.Conclusion. 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.

Urinary lipocalin‐2 is associated with renal disease activity in human lupus nephritis

“…Thus, defining an early and reliable biomarker of kidney involvement in SLE is highly desirable (29,30). Many urinary molecules have been proposed as LN biomarkers, but none has yet been validated nor has any been incorporated into routine practice (36)(37)(38)(39)(40)(41)(42)(43).…”

Polymorphisms in CCL2&CCL5 chemokines/chemokine receptors genes and their association with diseases

“…Two papers have reported an association of MCP-1-2518 A/G polymorphism with clinical manifestation of SLE in terms of renal involvement toward lupus nephritis 34,35 . In addition, Tucci et al suggest that an A/ G or G/G genotype may predispose to the development of SLE 35 .…”

Genetic studies of systemic lupus erythematosus in Asia: where are we now?

“…Proteinuria was reduced and survival was prolonged in an MCP-1-deficient MRL-lpr mouse model, suggesting that this gene has an important function in lupus nephritis. 177 The rs1024611 (À2518A/G) SNP of MCP-1 was positively associated with SLE susceptibility in Caucasians 178,179 and Mexicans 180 but not in Spaniards, 181,182 African Americans, 178 Koreans, 183,184 Japanese 185 and Chinese.…”