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


CONCLUSIONS
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.
Kanemitsu
Satomi
S
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. satomi@mailserver.med.kyushu-u.ac.jp
Ihara
Kenji
K
Saifddin
Ahmed
A
Otsuka
Takeshi
T
Takeuchi
Tsutomu
T
Nagayama
Jun
J
Kuwano
Michihiko
M
Hara
Toshiro
T
D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012016:Reference Values; D012680:Sensitivity and Specificity; D019014:fas Receptor / Q000235:genetics*
D019014:fas Receptor