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Polymorphisms of human CD19 gene: possible association with susceptibility to systemic lupus erythematosus in Japanese

Genes & Immunity volume 3, pages S21–S30 (2002)Cite this article

Abstract

CD19 regulates the signaling for B lymphocyte development, activation and proliferation. In mice, CD19 deficiency and overexpression were shown to result in hypogammaglobulinemia and autoantibody production, respectively. In the present study, we screened for the polymorphisms of CD19 , and examined the detected polymorphisms for the association with rheumatoid arthritis (RA), Crohn’s disease and systemic lupus erythematosus (SLE). Two SNPs, c.705G>T (P235P and IVS14-30C>T, were decreased (P = 0.0096 and P = 0.028, respectively), in SLE. A GT repeat polymorphism, c.*132(GT)12–18, was detected within the 3’-untranslated region, and individuals with ⩾15 times repeat was significantly increased in the independent two groups of Japanese SLE patients (P = 0.011 and P = 0.035, respectively); the overall difference between total SLE and controls was striking (P = 0.0061). No association was observed for RA and Crohn’s disease. In addition, no variations other than the common polymorphisms were detected in four patients with common variable immunodeficiency, the phenotype of which resembles CD19 deficient mice. In Caucasian SLE families, this GT repeat polymorphism was rare. CD19 mRNA level in the isolated peripheral blood B lymphocytes was lower in individuals possessing (GT)15–18 alleles compared with those without these alleles, both in controls and in SLE patients; however, the difference did not reach statistical significance. These results suggested that either the slight reduction in the CD19 mRNA level associated with the elongation of GT repeat, or an allele of another locus in linkage disquilibrium with CD19 (GT)15–18, may be associated with susceptibility to SLE in Japanese.

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Acknowledgements

The authors are indebted to Dr Shinichi Sato and Dr Makoto Inaoki (Department of Dermatology, Kanazawa University), Dr Manabu Fujimoto (International Medical Center of Japan), Mr Satoshi Makino and Mr Koichi Okamoto (Department of Genetic Information, Tokai University) for helpful discussions, to Dr Jun Ohashi (Department of Human Genetics, The University of Tokyo) for statistical analysis, to Dr Nelson Tsuno (Department of Transfusion Medicine, The University of Tokyo), Michiko Shiota, Tae Komata, Minae Kawashima, Aya Kawasaki and Chieko Kyogoku (Department of Human Genetics, The University of Tokyo) for helpful assistance and discussions.

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Authors and Affiliations

  1. Department of Human Genetics, The University of Tokyo, Tokyo, Japan

    K Kuroki & N Tsuchiya

  2. Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

    B P Tsao & J M Grossman

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

    T Fukazawa & H Hashimoto

  4. Department of Allergy and Rheumatology, The University of Tokyo, Tokyo, Japan

    K Hagiwara

  5. Department of Pediatrics, The University of Tokyo, Tokyo, Japan

    H Kano & T Iwata

  6. Division of Gastroenterology, Social Health Insurance Medical Center, Tokyo, Japan

    M Takazoe

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  1. K Kuroki
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Correspondence to N Tsuchiya.

Additional information

This study was supported by Grant-in-Aid for Scientific Research on Priority Areas (C), Grants-in-Aid for Scientific Research (B) from the Ministry of Education, Culture, Sports, Science and Technology, and a grant from the Ministry of Health, Labour and Welfare. New polymorphisms described in this study have been deposited in GenBank/ EMBL/ DDBJ accession No. AB052799, AB052814, AB052815, AB052816, AB052817 and AB052818.

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Kuroki, K., Tsuchiya, N., Tsao, B. et al. Polymorphisms of human CD19 gene: possible association with susceptibility to systemic lupus erythematosus in Japanese. Genes Immun 3 (Suppl 1), S21–S30 (2002). https://doi.org/10.1038/sj.gene.6363906

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