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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, and TOSHIRO HARA
ABSTRACT.
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. (J Rheumatol 2002;29:1183-8) Key Indexing Terms:
FAS PROMOTER GENE
From the Departments of Pediatrics, Internal Medicine I, and Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, and Department of Internal Medicine II, Saitama Medical Center, Saitama Medical School, Saitama, Japan. S. Kanemitsu, MD; K. Ihara, MD, PhD; A. Saifddin, MD, PhD; T. Hara, MD, PhD, Department of Pediatrics; T. Otsuka, MD, PhD, Department of Internal Medicine I; J. Nagayama, MD, PhD; M. Kuwano, MD, PhD, Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University; T. Takeuchi, MD, PhD, Department of Internal Medicine II, Saitama Medical Center, Saitama Medical School. Address reprint requests to Dr. S. Kanemitsu, Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail : satomi@mailserver.med.kyushu-u.ac.jp Submitted April 5, 2001; revision accepted December 6, 2001. |