Original Article | Published:

Association of single-nucleotide polymorphisms in the polymeric immunoglobulin receptor gene with immunoglobulin A nephropathy (IgAN) in Japanese patients

Journal of Human Genetics volume 48, pages 293299 (2003) | Download Citation

Abstract

Immunoglobulin A nephropathy (IgAN) is a primary glomerulonephritis of common incidence world-wide whose etiology and pathogenesis remain unresolved, although genetic factors are assumed to be involved in the development and progression of this disease. To identify genetic variations that might confer susceptibility to IgAN, we performed a case-control association study involving 389 Japanese IgAN patients and 465 controls. Genome-wide analysis of approximately 80,000 single-nucleotide polymorphisms (SNPs) identified a significant association between IgAN and six SNPs located in the PIGR (polymeric immuoglobulin receptor) gene at chromosome 1q31-q41. One of them, PIGR-17, caused an amino-acid substitution from alanine to valine at codon 580 (χ2=13.05, P=0.0003, odds ratio [OR] =1.59, 95% confidence interval [95% CI] =1.24–2.05); the OR of minor homozygotes to others was 2.71 (95% CI = 1.31–5.61). Another SNP, PIGR-2, could affect promoter activity (χ2 = 11.95, P=0.00055, OR=1.60, 95% CI=1.22–2.08); the OR of minor homozygotes to others was 2.08 (95% CI=0.94–4.60). Pairwise analyses demonstrated that all six SNPs were in almost complete linkage disequilibrium. Biopsy specimens from IgAN patients were positively stained by antibody against the secretory component of PIGR, but corresponding tissues from non-IgAN patients were not. Our results suggest that a gene associated with susceptibility to IgAN lies within or close to the PIGR gene locus on chromosome 1q in the Japanese population.

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Affiliations

  1. Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo, Japan

    • Wataru Obara
    • , Fumihiro Akiyama
    • , Satoru Miyano
    •  & Yusuke Nakamura
  2. Department of Urology, Iwate Medical University, Iwate, Japan

    • Wataru Obara
    • , Yasushi Suzuki
    •  & Tomoaki Fujioka
  3. Laboratory for Genotyping, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan

    • Aritoshi Iida
  4. Laboratory for Cardiovascular Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan

    • Toshihiro Tanaka
    •  & Yozo Ohnishi
  5. Laboratory for Diabetic Nephropathy, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan

    • Shiro Maeda
  6. Laboratory for Rheumatic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan

    • Ryo Yamada
  7. Laboratory for Medical Informatics, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan

    • Tatsuhiko Tsunoda
  8. Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan

    • Takashi Takei
    • , Kyoko Ito
    • , Kazuho Honda
    • , Keiko Uchida
    • , Ken Tsuchiya
    • , Wako Yumura
    • , Kosaku Nitta
    •  & Hiroshi Nihei
  9. Department of Urology, Iwate Prefectural Ofunato Hospital, Iwate, Japan

    • Takashi Ujiie
  10. Department of Urology, Sanai Hospital, Iwate, Japan

    • Yutaka Nagane
  11. Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    • Ichiei Narita
    •  & Fumitake Gejyo
  12. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-639, Japan

    • Yusuke Nakamura

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Corresponding author

Correspondence to Yusuke Nakamura.

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DOI

https://doi.org/10.1007/s10038-003-0027-1