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Journal of Human Genetics

, Volume 48, Issue 6, pp 293–299 | Cite as

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

  • Wataru Obara
  • Aritoshi Iida
  • Yasushi Suzuki
  • Toshihiro Tanaka
  • Fumihiro Akiyama
  • Shiro Maeda
  • Yozo Ohnishi
  • Ryo Yamada
  • Tatsuhiko Tsunoda
  • Takashi Takei
  • Kyoko Ito
  • Kazuho Honda
  • Keiko Uchida
  • Ken Tsuchiya
  • Wako Yumura
  • Takashi Ujiie
  • Yutaka Nagane
  • Kosaku Nitta
  • Satoru Miyano
  • Ichiei Narita
  • Fumitake Gejyo
  • Hiroshi Nihei
  • Tomoaki Fujioka
  • Yusuke NakamuraEmail author
Original Article
  • 90 Downloads

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.

Keywords

Single-nucleotide polymorphism IgA nephropathy Polymeric immunoglobulin receptor 

Notes

Acknowledgements

We gratefully acknowledge assistance from Susumu Saito, Akihiro Sekine, and technicians at the SNP Research Center, The Institute of Physical and Chemical Research (RIKEN). This work was supported in part by a "Research for the Future" Program Grant of the Japan Society for the Promotion of Science to Y.N.

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Copyright information

© The Japan Society of Human Genetics and Springer-Verlag 2003

Authors and Affiliations

  • Wataru Obara
    • 1
    • 2
  • Aritoshi Iida
    • 3
  • Yasushi Suzuki
    • 2
  • Toshihiro Tanaka
    • 4
  • Fumihiro Akiyama
    • 1
  • Shiro Maeda
    • 5
  • Yozo Ohnishi
    • 4
  • Ryo Yamada
    • 6
  • Tatsuhiko Tsunoda
    • 7
  • Takashi Takei
    • 8
  • Kyoko Ito
    • 8
  • Kazuho Honda
    • 8
  • Keiko Uchida
    • 8
  • Ken Tsuchiya
    • 8
  • Wako Yumura
    • 8
  • Takashi Ujiie
    • 9
  • Yutaka Nagane
    • 10
  • Kosaku Nitta
    • 8
  • Satoru Miyano
    • 1
  • Ichiei Narita
    • 11
  • Fumitake Gejyo
    • 11
  • Hiroshi Nihei
    • 8
  • Tomoaki Fujioka
    • 2
  • Yusuke Nakamura
    • 1
    • 12
    Email author
  1. 1.Human Genome Center, The Institute of Medical ScienceUniversity of TokyoJapan
  2. 2.Department of UrologyIwate Medical UniversityIwateJapan
  3. 3.Laboratory for Genotyping, SNP Research CenterThe Institute of Physical and Chemical Research (RIKEN)TokyoJapan
  4. 4.Laboratory for Cardiovascular Diseases, SNP Research CenterThe Institute of Physical and Chemical Research (RIKEN)TokyoJapan
  5. 5.Laboratory for Diabetic Nephropathy, SNP Research CenterThe Institute of Physical and Chemical Research (RIKEN)TokyoJapan
  6. 6.Laboratory for Rheumatic Diseases, SNP Research CenterThe Institute of Physical and Chemical Research (RIKEN)TokyoJapan
  7. 7.Laboratory for Medical Informatics, SNP Research CenterThe Institute of Physical and Chemical Research (RIKEN)TokyoJapan
  8. 8.Department of Medicine, Kidney CenterTokyo Women's Medical UniversityTokyoJapan
  9. 9.Department of UrologyIwate Prefectural Ofunato HospitalIwateJapan
  10. 10.Department of UrologySanai HospitalIwateJapan
  11. 11.Division of Clinical Nephrology and RheumatologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
  12. 12.Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical ScienceUniversity of TokyoTokyo 108–8639 Japan

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