Monocyte chemoattractant protein-1: plasma concentrations and A(-2518)G promoter polymorphism of its gene in systemic lupus erythematosus

• Published in: Journal of rheumatology 2007-04, Vol.34 (4), p.740-746
• Main Authors: BROWN, Karen S, NACKOS, Eleni, MORTHALA, Suneetha, JENSEN, Liselotte E, WHITEHEAD, Alexander S, VON FELDT, Joan M
• Format: Article
• Language: English
• Subjects: Adult; African Americans; Biological and medical sciences; Calcinosis - immunology; Case-Control Studies; Chemokine CCL2 - blood; Chemokine CCL2 - genetics; Coronary Vessels - pathology; European Continental Ancestry Group; Female; Genetic Predisposition to Disease - genetics; Homocysteine - blood; Humans; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - ethnology; Lupus Erythematosus, Systemic - genetics; Medical sciences; Middle Aged; Nephritis - blood; Nephritis - genetics; Nephritis - immunology; Polymorphism, Single Nucleotide; Promoter Regions, Genetic - genetics; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
• ISSN: 0315-162X; 1499-2752

OBJECTIVE: To determine (1) whether the A(-2518)G polymorphism of CCL-2, the gene encoding monocyte chemoattractant protein-1 (MCP-1), is associated with disease, MCP-1 concentration, nephritis, or coronary artery calcification (CAC) in systemic lupus erythematosus (SLE); and (2) whether MCP-1 and homocysteine (Hcy) concentrations are correlated. METHODS: Statistical tests were applied to determine the relationships between CCL-2 A(-2518)G genotypes, plasma MCP-1 concentrations, and clinical variables in Caucasian and African American patients with SLE and controls. RESULTS: The CCL-2 (-2518)G allele was not significantly associated with SLE in the whole study sample (p = 0.07). Among Caucasians, but not African Americans, G allele carriers had significantly increased risk of SLE (OR 4.2, 95% CI 1.8-9.6, p < 0.0001). Genotype was not associated with nephritis, CAC, or MCP-1 concentrations when all patients or all controls were considered; however, among recently diagnosed patients, G allele carriers had significantly higher MCP-1 concentrations than AA homozygotes (p = 0.02). SLE patients had higher MCP-1 concentrations than controls (p < 0.0001), African American patients had higher concentrations than Caucasian patients (p = 0.006), and patients with nephritis had higher concentrations than those without nephritis (p = 0.02). Although not associated with CAC, MCP-1 concentrations were significantly positively correlated with Hcy. CONCLUSION. CCL-2 A(-2518)G genotype is a significant risk factor for SLE among Caucasians but not African Americans, suggesting that genetically mandated differences in MCP-1 expression contribute to SLE etiology in the former. The positive correlation between MCP-1 and Hcy concentrations is consistent with the hypothesis that active inflammation and hyperhomocysteinemia are etiologically linked.