The Glucocorticoid Receptor Gene Polymorphism in Patients with Systemic Lupus Erythematosus: Association of Polymorhpism with Clinical Characteristics

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14570430
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 内科学一般
• Research Institution: JUNTENDO UNIVERSITY
• Principal Investigator: FUKAZAWA Toru JUNTENDO UNIVERSITY, rheumatology, assistant professor, 医学部, 講師 (30301500)
• Project Period (FY): 2002 – 2003
• Keywords: Systemic lupus erythematosus / Steroid resistance / The human glucocorticoid receptor / anti-Sm antibody / Polymorphisms of the human glucocorticoid receptor

Research Abstract

Objectiv. The study investigated and evaluated polymorhisms of the glucocorticoid receptor(GR) gene in SLE patients and the association of GR polymorhisms with clinical characteristic features and glucocorticoid resistance.
Methods. A total of 166 Japanese systemic lupus erythematosus(SLE) patients (9 males and 157 females between the ages of 15-71 years; mean ア S.D. :38.5±12.4) and 52 Japanese controls (26 males and 26 females between ages of 20-38 years; mean ± S.D. :27.7 ± 3.8) were examined. Genotyping of exon7 and exon8, which are located in the C-terminal ligand-binding domain of the GR gene were performed with the direct sequencing method. Genotyping of exon2,3,4,5,6,9 a were performed in randomly selected 32 patients with SLE. In addition We analyzed the association of GR polymorhisms and clinical characteristic features.
Results. 1)The GR single nucleotide polymorhisms(SNP) in exon 8,2166 C>T(D678D), was indentified in SLE patients and the controls. 2)Siginiaicantly higher frequency of 2166 C/T genotype was detected in SLE patients (15.7%, odds ratio 4.81,P=0.035) than in the controls(3.8%). 3)The four GR SNPs in up-stream of exon5 and exon6,8,9α was indentified in SLE patients and the Linkage Disequilibrium among those SNPs and 2166 C>T was observed..4) Siginiaicantly higher 2166 C/T genotype frequency in SLE patients with anti-Sm antibody (P=0.012) was revealed. 5)2166 C/T genotype was not associated with steroid resistance.
Conclusion. We detected and confirmed GR SNP in the LBD, 2166 C>T(D678D),and the frequency of 2166 C/T genotype was siginiaicantly higher in SLE patients than in controls. The frequency of 2166 C/Tgenotype was identified to be siginiaicantly higher in SLE patients with anti-Sm antibodies but not associated with glucocorticoid resistance. In addition, The Linkage Disequilibrium among 2166 C/Tgenotype and four other SNPs was observed.