Tohoku. J. Exp. Med., 2004, 203(2)

A Mutation of the Glucocorticoid Receptor Gene in Patients with Systemic Lupus Erythematosus

YOUNG MOO LEE, JUNKO FUJIWARA,¹ YASUHIKO MUNAKATA,² TOMONORI ISHII,² AKIRA SUGAWARA,³ MITSUO KAKU,1 SHOICHI KOKUBUN, TAKESHI SASAKI² and TADAO FUNATO¹

Department of Orthopedics, ¹Department of Molecular Diagnostics, ²Department of Rheumatology and Hematology, and ³Department of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University, School of Medicine, Sendai 980-8574

We screened for mutations of the glucocorticoid receptor (GR) gene in patients with systemic lupus erythematosus (SLE), a typical autoimmune disease. Polymerase chain reaction-single-strand conformation polymorphism analysis (PCR-SSCP) revealed a single mutation in exon 9 of the GR gene in 11/132 (8.3%) among 66 patients with SLE. No mutations were detected in 52 healthy individuals (0/104, 0.0%), but the same mutation was detected in other autoimmne diseases (4/108, 3.7%). DNA sequencing showed a T to C substitution at codon 766 (position 2430) of the GR gene, which does not alter the amino acid sequence of the GR. Further analysis using a LightCycler generated different melting curves indicates that the pattern with this mutation is different from that of wild type. The identified mutation of the GR gene may represent a polymorphism associated with SLE.

keywords —— glucocorticoid receptor (GR); mutation; systemic lupus erythematosus (SLE); polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP); LightCycler

© 2004 Tohoku University Medical Press

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Address for reprints: Tadao Funato, M.D., Department of Molecular Diagnostics, Tohoku University, School of Medicine, 1-1 Seiryomachi, Aoba-ku, Sendai 980-8574, Japan.

e-mail: tfunato@mail.tains.tohoku.ac.jp