Home

Current Issue

Archives

Guidelines for Authors

Classified Ads

Links

Search PubMed

Subscriptions

Subscriber Registration

Guidelines for Website Users

JRheum Update Service

Contact Info

JIM C. OATES, MARC C. LEVESQUE, MAURINE R. HOBBS, ERICA GRACE SMITH, IVAN D. MOLANO, GRIER P. PAGE, BRUCE S. HILL, J. BRICE WEINBERG, GLINDA S. COOPER, and GARY S. GILKESON

ABSTRACT.

Objective. Systemic lupus erythematosus (SLE) is an autoimmune disease in which morbidity and mortality are higher in African-Americans. The etiology of this racial disparity is unknown. A genetic predisposition to enhanced nitric oxide (NO) production may predispose African-Americans to develop SLE and may increase disease severity. We have demonstrated a correlation between NO production and disease activity in SLE. Two polymorphisms in the inducible NO synthase (NOS2) promoter region (G-954C and CCTTT microsatellite repeat polymorphisms) are associated with improved outcome in some African patients with malaria. This study was designed to determine if these polymorphisms are associated with SLE.

Methods. We assessed the frequency of both the G-954C and CCTTT microsatellite repeat NOS2 promoter polymorphisms in a cohort of patients with SLE and age, sex, and race matched controls in North Carolina and South Carolina.

Results. Both polymorphisms were more frequent among African-American female SLE patients when compared with controls (p = 0.04 for the G-954C polymorphism and p = 0.03 for the CCTTT-8 repeat polymorphism). Further, the G-954C and CCTTT-8 repeat polymorphisms were in linkage disequilibrium (D¢ = 0.89, p = 0.0001) among African-American female SLE patients.

Conclusion. Altered genetic control of NOS2 transcription may be a risk factor for SLE among African-American females. The extent of linkage disequilibrium between the G-954C and CCTTT-8 repeat NOS2 promoter polymorphisms suggests that they were co-inherited. (J Rheumatol 2003;30:60-7)

Key Indexing Terms:

BLACKS
POLYMORPHISM (GENETICS)
MICROSATELLITE REPEATS
PROMOTER REGIONS (GENETICS)
GENETIC PREDISPOSITION TO DISEASE

Supported by VA Career Development Award, VA REAP Award, the VA Medical Research Service; NIH grants AR45476, AR39162, and AI41764; Medical University of SC University Research Committee Award; and Intramural Research Program of the National Institute of Environmental Health Sciences.

J.C. Oates, MD, Assistant Professor of Medicine, Ralph H. Johnson VAMC, Medical University of SC; M.C. Levesque, MD, PhD, Assistant Professor of Medicine, Durham VAMC, Duke University Medical Center; M.R. Hobbs, PhD, Assistant Professor of Internal Medicine and Human Genetics, Department of Internal Medicine, University of Utah School of Medicine; E.G. Smith, BS, Medical Student; I.D. Molano, BS, Technician, Ralph H. Johnson VAMC; G.P. Page, PhD, Assistant Professor of Biostatistics, Department of Biostatistics, University of Alabama; B.S. Hill, MD, private practitioner, Center for Arthritis and Rheumatic Diseases; J.B. Weinberg, MD, Professor of Medicine and Immunology, Department of Medicine, Durham VAMC, Duke University School of Medicine; G.S. Cooper, PhD, Investigator, NIEHS; G.S. Gilkeson, MD, Professor of Medicine, Department of Medicine, Ralph H. Johnson VAMC and Medical University of South Carolina.

Address reprint requests to Dr. J. Oates, 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: oatesjc@musc.edu

Submitted January 21, 2002; revision accepted July 15, 2002.