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Association of the G-463A Myeloperoxidase Gene Polymorphism with Renal Disease in African Americans with Systemic Lupus Erythematosus

HENDA BOUALI, PAUL NIETERT, TAMARA M. NOWLING, JANARDAN PANDEY, MARY ANNE DOOLEY, GLINDA COOPER, JOHN HARLEY, DIANE L. KAMEN, JIM OATES, and GARY GILKESON

ABSTRACT.

Objective. Myeloperoxidase (MPO) is an enzyme expressed in neutrophils that is involved in tissue damage in inflammatory renal diseases. A functional G to A single-nucleotide polymorphism (SNP) is present at position –463 of the MPO promoter region and is associated with altered MPO expression. We hypothesized that the G-463A MPO SNP is a risk factor for developing lupus nephritis (LN) due to its potential influence on the inflammatory response.

Methods. DNA from 229 patients with SLE and 277 controls from the Carolina Lupus cohort, 58 African American patients from the Sea Island Lupus Cohort, and 51 African American patients from the Lupus Multiplex Registry and Repository were genotyped by PCR. A linear regression model was used to examine relationships between the MPO genotype, case/control status, demographic characteristics, and LN.

Results. There was no association of MPO genotype with systemic lupus erythematosus (SLE). However, the odds of developing LN were significantly higher among those with an A allele, compared to those without, in African American cases of all 3 cohorts. When the likelihood of developing LN was compared across MPO genotypes, the risk of developing LN was significantly higher among cases with a GA genotype versus GG (OR 2.11, 95% CI 1.12 to 3.97) and even higher with AA versus GG (OR 3.52, 95% CI 1.41 to 8.77).

Conclusion. While the G-463A MPO SNP is not a risk factor for developing SLE, the low expressing A allele is a significant risk factor for developing LN that is gene dosage-dependent in African Americans. (First Release Sept 15 2007; J Rheumatol 2007;34:2028-34)

Key Indexing Terms:

SYSTEMIC LUPUS ERYTHEMATOSUS
MYELOPEROXIDASE
POLYMORPHISM
AFRICAN AMERICAN
LUPUS NEPHRITIS

From the Department of Medicine, Division of Rheumatology, Medical University of South Carolina, Charleston, South Carolina, USA.

Supported by Medical University of South Carolina General Clinical Research Center, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health grants P60 AR049459 and AR47469; and the Lupus Multiplex Registry and Repository.

H. Bouali, MD, Rheumatology Fellow; P. Nietert, PhD, Assistant Professor; T.M. Nowling, PhD, Assistant Professor; J. Pandey, PhD, Professor; J. Oates, MD, Assistant Professor; D.L. Kamen, MD, MSCR, Assistant Professor, Medical University of South Carolina; M.A. Dooley, MD, Associate Professor, Department of Medicine, University of North Carolina Affiliated Hospitals; G. Cooper, PhD, National Institutes of Environmental Health Sciences, Research Triangle Park, North Carolina; J. Harley, MD, PhD, Professor, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma; G. Gilkeson, MD, Professor of Medicine, Chief of Rheumatology, Ralph H. Johnson VA Medical Center, Charleston, SC.

Address reprint requests to Dr. G. Gilkeson, Department of Medicine, Division of Rheumatology, Medical University of South Carolina, 96 Jonathan Lucas St., Suite 912, PO Box 250623, Charleston, SC 29425. E-mail: gilkeson@musc.edu

Accepted for publication June 25, 2007.