A functional polymorphism in Fas (CD95/APO-1) gene promoter associated with systemic lupus erythematosus

Satomi Kanemitsu, Kenji Ihara, Ahmed Saifddin, Takeshi Otsuka, Tsutomu Takeuchi, Jun Nagayama, Michihiko Kuwano, Toshiro Hara

Research output: Contribution to journalArticlepeer-review

126 Citations (Scopus)


Objective. To investigate whether Fas promoter polymorphisms show a genetic contribution to the development of systemic lupus erythematosus (SLE) in a Japanese population, and to study the functional difference in promoter activity of the polymorphisms. Methods. In 109 SLE patients and 140 controls, the frequencies of A/G polymorphisms at -670 nucleotide position and G/A at -1377 nucleotide position were determined by allele-specific polymerase chain reaction (PCR) or PCR-single strand conformation polymorphism analysis. The functional significance of the -670A/G polymorphism in the Fas gene was evaluated by a combination of Fas transcriptional activity in the reporter gene assay and binding activity of signal transducer and activator of transcription (STAT)1 protein in the electrophoretic mobility shift assay. Results. SLE patients exhibited significantly higher frequency of A allele at nucleotide position -670 (p = 0.004). There was no significant difference in the nucleotide position -1377 in Fas promoter gene between SLE patients and controls. The electrophoretic mobility shift assay demonstrated that the oligonucleotide with -670A in the Fas promoter had a higher binding ability to a GAS binding protein, STAT1, than that with -670G, although there was no statistically significant difference in the reporter gene assay. Conclusion. Fas promoter -670A/G polymorphism was significantly associated with SLE, suggesting a possibility that Fas promoter contributes, at least in part, to the pathogenesis of SLE.

Original languageEnglish
Pages (from-to)1183-1188
Number of pages6
JournalJournal of Rheumatology
Issue number6
Publication statusPublished - 2002
Externally publishedYes


  • Fas promoter gene
  • Polymorphism
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'A functional polymorphism in Fas (CD95/APO-1) gene promoter associated with systemic lupus erythematosus'. Together they form a unique fingerprint.

Cite this