Monocyte chemoattractant protein-1: plasma concentrations and A(-2518)G promoter polymorphism of its gene in systemic lupus erythematosus.
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.
Brown
Karen S
KS
Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Nackos
Eleni
E
Morthala
Suneetha
S
Jensen
Liselotte E
LE
Whitehead
Alexander S
AS
Von Feldt
Joan M
JM
D000328:Adult; D001741:Black or African American; D002114:Calcinosis / Q000276:immunology; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics*; D003331:Coronary Vessels / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000208:ethnology / Q000235:genetics*; D008875:Middle Aged; D009393:Nephritis / Q000097:blood / Q000235:genetics / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D044465:White People
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D006710:Homocysteine