PT - JOURNAL ARTICLE AU - Satomi Kanemitsu AU - Kenji Ihara AU - Ahmed Saifddin AU - Takeshi Otsuka AU - Tsutomu Takeuchi AU - Jun Nagayama AU - Michihiko Kuwano AU - Toshiro Hara TI - A functional polymorphism in fas (CD95/APO-1) gene promoter associated with systemic lupus erythematosus. DP - 2002 Jun 01 TA - The Journal of Rheumatology PG - 1183--1188 VI - 29 IP - 6 4099 - http://www.jrheum.org/content/29/6/1183.short 4100 - http://www.jrheum.org/content/29/6/1183.full SO - J Rheumatol2002 Jun 01; 29 AB - 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.