Objectives: This study was undertaken to investigate the possible association of Fas gene mutation(s) or polymorphism(s) with systemic lupus erythematosus (SLE) in Japanese.
Methods: Screening for structural defects of the Fas gene was performed by using reverse transcriptase-polymerase chain reaction (RT-PCR)/single-strand conformation polymorphism (SSCP) analysis in 57 patients with SLE, followed by direct sequencing for the aberrantly migrating bands. The frequency of Fas polymorphism was determined by sequence-specific oligonucleotide probe (SSOP) hybridization in 82 SLE patients and 132 ethnically matched healthy individuals.
Results: We found a novel polymorphism at nucleotide 297 (T297C), which was linked to Fas polymorphism at nucleotide 416 (A416G). The 297C/416G genotype was present in four of the 132 (3.0%) healthy controls, none of whom was homozygous for the genotype. The allele frequency for 297C/416G in the controls was 1.5%. In contrast, 10 of the 82 (12.2%) SLE patients carried the 297C/416G allele, including one patient homozygous for the genotype. The allele frequency in SLE patients was 6.7%. The 297C/416G allele was significantly frequent in SLE patients (P = 0.01, chi2) with a relative risk of 5.00.
Conclusion: As the polymorphism 297C/416G is silent at the amino acid level, it may affect the expression of Fas itself or be linked to a neighbouring genetic abnormality that is responsible for the pathogenesis of SLE.