Objective. We investigated the association of gene polymorphisms in APRIL, a new member of the TNF family, with systemic lupus erythematosus. Methods. To detect polymorphisms of the human APRIL gene by exon-specific polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis, we first determined the structure of the human APRIL gene. We designed exon-specific oligonucleotide primers according to the genomic DNA sequence of APRIL. All of the coding regions in exons of the APRIL gene were analysed by exon-specific PCR-SSCP in 148 SLE patients and 146 unaffected controls, then the nucleotide sequences of exons that displayed aberrant bands were determined. Results. The human APRIL gene comprised at least six exons with five introns, spanning approximately 2.8 kilobases of the genomic DNA. By exon-specific PCR-SSCP, we identified two novel polymorphisms at codons 67 and 96. Both had amino acid substitutions: G67R and N96S respectively. Only the 67G allele was associated with SLE in 148 Japanese SLE patients, with allele frequency 0.662 compared with 0.575 for 146 unaffected controls (P = 0.0302). The frequency of the individuals who possessed at least one 67G allele in SLE patients (91.9%) was significantly higher than that in the unaffected controls (80.1%) (P = 0.0036). Conclusion. The 67G allele of APRIL may be a contributing factor in the pathogenesis of SLE.
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