Association of Fas/APO-1 gene polymorphism with systemic lupus erythematosus in Japanese

Objectives. This study was undertaken to investigate the possible associati on of Fas gene mutation(s) or polymorphism(s) with systemic lupus erythemat osus (SLE) in Japanese. Methods. Screening for structural defects of the Fas gene was performed by using reverse transcriptase-polymerase chain reaction (RT-PCR)/single-stran d conformation polymorphism (SSCP) analysis in 57 patients with SLE, follow ed by direct sequencing for the aberrantly migrating bands. The frequency o f Fas polymorphism was determined by sequence-specific oligonucleotide prob e (SSOP) hybridization in 82 SLE patients and 132 ethnically matched health y individuals. Results. We found a novel polymorphism at nucleotide 297 (T297C), which was linked to Fas polymorphism at nucleotide 416 (A416G). The 297C/416G genoty pe 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 con trols 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 al lele frequency in SLE patients was 6.7%. The 297C/416G allele was significa ntly frequent in SLE patients (P = 0.01, chi(2)) 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.