Analysis on the association of human BLYS (BAFF TNFSF13B) polymorphisms with systemic lupus erythematosus and rheumatoid arthritis

Recent studies indicated a substantial role of BLyS (BAFF, TNFSF13B) in the pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in humans and in animal models. This study was conducted to screen for polymorphisms of human BLYS, and to examine whether they are involved in the genetic susceptibility to human SLE and RA. A systematic polymorphism screening was performed in the coding region, 5' and 3' untranslated regions, and promoter region of human BLYS. Association of the detected polymorphisms with SLE and RA was analyzed in 221 Japanese patients with RA, 156 with SLE, and 227 healthy individuals, using the case-control approach. Four single nucleotide polymorphisms (SNPs) in the promoter, one SNP in intron 1, and one rare nonsynonymous substitution (Ala105Thr) in the coding region were detected. The BLYS SNPs were found to form three common haplotypes. Significant association with the susceptibility to SLE or RA was not observed. However, a tendency for the increase of - 871T/T genotype was observed in SLE patients with anti-Sm antibody (P = 0.082). BLYS mRNA level was significantly elevated in the monocytes from individuals carrying - 871T (P = 0.010). In addition, although statistically not significant, 105Thr allele was slightly increased in patients with RA compared with controls (P = 0.058). Characterizing the functional and clinical significance of these new SNPs requires further study.