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

Genes & Immunity volume 3, pages 424–429 (2002)Cite this article

Abstract

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.

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Acknowledgements

The authors are indebted to Dr Jun Ohashi (Department of Human Genetics, The University of Tokyo) for statistical analysis, Dr Kunio Matsuta (Matsuta Clinic) for the recruitment of the patients, Dr Manabu Fujimoto (Department of Regenerative Medicine, Research Institute, International Medical Center of Japan), Dr Takeshi Suzuki (Department of Allergy and Rheumatology, The University of Tokyo) and Daisuke Sakurai (Department of Human Genetics, The University of Tokyo) for valuable suggestions.

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Authors and Affiliations

  1. Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    A Kawasaki, N Tsuchiya & K Tokunaga

  2. Department of Rheumatology and Internal Medicine, Juntendo University, Tokyo, Japan

    T Fukazawa & H Hashimoto

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  1. A Kawasaki
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  2. N Tsuchiya
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  3. T Fukazawa
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  4. H Hashimoto
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  5. K Tokunaga
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Correspondence to N Tsuchiya.

Additional information

This study was supported by the Grant-in-Aid for Scientific Research on Priority Areas (C) ‘Medical Genome Science’, the Grant-in-Aid for Scientific Research (B) from the Ministry of Education, Science, Sports and Culture of Japan, and grants from the Ministry of Health, Labour and Welfare of Japan.

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Kawasaki, A., Tsuchiya, N., Fukazawa, T. et al. Analysis on the association of human BLYS (BAFF, TNFSF13B) polymorphisms with systemic lupus erythematosus and rheumatoid arthritis. Genes Immun 3, 424–429 (2002). https://doi.org/10.1038/sj.gene.6363923

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