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F. YESIM K. DEMIRCI, SUSAN MANZI, ROSALIND RAMSEY-GOLDMAN, MARGARET KENNEY, PENNY S. SHAW, CHARMAYNE M. DUNLOP-THOMAS, AMY H. KAO, ELISA Y. RHEW, FRANKLIN BONTEMPO, CANDACE KAMMERER, and M. ILYAS KAMBOH

ABSTRACT.

Objective. Toll-like receptors (TLR) play an important role in both adaptive and innate immunity. Variations in TLR genes have been shown to be associated with various infectious and inflammatory diseases. We investigated the association of TLR5 (Arg392Stop, rs5744168) and TLR9 (–1237T→C, rs5743836) single nucleotide polymorphisms (SNP) with systemic lupus erythematosus (SLE) in Caucasian American subjects.

Methods. We performed a case-control association study and genotyped 409 Caucasian women with SLE and 509 Caucasian healthy female controls using TaqMan^® allelic discrimination (rs5744168) or polymerase chain reaction-restriction fragment length polymorphism analysis (rs5743836).

Results. None of the 2 TLR SNP showed a statistically significant association with SLE risk in our cohort.

Conclusion. Our results do not indicate a major influence of these putative functional TLR SNP on the susceptibility to (or protection from) SLE. (First Release May 15 2007; J Rheumatol 2007;34:1708-11)

Key Indexing Terms:

TLR5
TLR9
TOLL-LIKE RECEPTOR
LUPUS
SYSTEMIC LUPUS ERYTHEMATOSUS

From the Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania; Division of Rheumatology and Clinical Immunology, Lupus Center of Excellence, University of Pittsburgh, Pittsburgh, Pennsylvania; Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; and Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Supported by the National Heart, Lung, and Blood Institute grants HL074165 and HL54900; National Institute of Arthritis and Musculoskeletal and Skin Diseases grants AR46588, AR002213, AR02318, AR48098, F32 AR51681; and NIH General Clinical Research Center grants M01-RR000056 and M01-RR000048.

F.Y.K. Demirci, MD, Research Assistant Professor; M. Kenney, MS, Research IV; C. Kammerer, PhD, Associate Professor; M.I. Kamboh, PhD, Professor, Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh; S. Manzi, MD, MPH, Associate Professor; P.S. Shaw, RN, Clinical Research Coordinator; A.H. Kao, MD, MPH, Assistant Professor, Division of Rheumatology and Clinical Immunology, Lupus Center of Excellence, University of Pittsburgh; R. Ramsey-Goldman, MD, DrPH, Professor; C.M. Dunlop-Thomas, MS, Lead Research Coordinator; E.Y. Rhew, MD, MSCI, Instructor, Division of Rheumatology, Feinberg School of Medicine, Northwestern University; F. Bontempo, MD, Associate Professor, Department of Medicine, School of Medicine, University of Pittsburgh.

Address reprint requests to Prof. M.I. Kamboh, Department of Human Genetics, Graduate School of Public Health, Pittsburgh, PA 15261. E-mail: ikamboh@hgen.pitt.edu

Accepted for publication March 6, 2007.