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

J Rheumatol. 2002 Jun;29(6):1183-8.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Alleles
  • Base Sequence
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Humans
  • Japan
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic
  • Reference Values
  • Sensitivity and Specificity
  • fas Receptor / genetics*

Substances

  • fas Receptor