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KAREN S. BROWN, ELENI NACKOS, SUNEETHA MORTHALA, LISELOTTE E. JENSEN, ALEXANDER S. WHITEHEAD, and JOAN M. VON FELDT

ABSTRACT.

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. (J Rheumatol 2007;34:740-6)

Key Indexing Terms:

MONOCYTE CHEMOATTRACTANT PROTEIN-1
INFLAMMATORY DISEASE
CCL-2
NEPHRITIS
HOMOCYSTEINE
SYSTEMIC LUPUS ERYTHEMATOSUS

From the Department of Pharmacology and Center for Pharmacogenetics, and Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

Supported by grants from the Lupus Research Institute and the American Heart Association (J.M. Von Feldt), by NIH grant AR47663 (A.S. Whitehead), and by the General Clinical Research Center of the University of Pennsylvania. K.S. Brown was supported by a grant from the American Heart Foundation.

K.S. Brown, PhD (current address: Daiichi Sankyo Pharma Development, 399 Thornall Street, Edison, NJ 08837, USA); L.E. Jensen, PhD;
A.S. Whitehead, DPhil, Department of Pharmacology and Center for Pharmacogenetics; E. Nackos, BS; S. Morthala, MD; J.M. Von Feldt, MD, Department of Medicine, University of Pennsylvania School of Medicine.

Address reprint requests to Dr. J.M. Von Feldt, Division of Rheumatology, Department of Medicine, University of Pennsylvania, 5 Maloney,
Suite 504, 3600 Spruce Street, Philadelphia, PA 19104, USA.
E-mail: vonfeldt@mail.med.upenn.edu

Accepted for publication November 22, 2006.