Association of single-nucleotide polymorphisms in the polymeric immunoglobulin receptor gene with immunoglobulin A nephropathy (IgAN) in Japanese patients.
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 (chi(2)=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 (chi(2)=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.
Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.|Department of Urology, Iwate Medical University, Iwate, Japan.
Wataru
W
Obara
Laboratory for Genotyping, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
Aritoshi
A
Iida
Department of Urology, Iwate Medical University, Iwate, Japan.
Yasushi
Y
Suzuki
Laboratory for Cardiovascular Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
Toshihiro
T
Tanaka
Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Fumihiro
F
Akiyama
Laboratory for Diabetic Nephropathy, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
Shiro
S
Maeda
Laboratory for Cardiovascular Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
Yozo
Y
Ohnishi
Laboratory for Rheumatic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
Ryo
R
Yamada
Laboratory for Medical Informatics, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
Tatsuhiko
T
Tsunoda
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Takashi
T
Takei
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Kyoko
K
Ito
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Kazuho
K
Honda
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Keiko
K
Uchida
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Ken
K
Tsuchiya
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Wako
W
Yumura
Department of Urology, Iwate Prefectural Ofunato Hospital, Iwate, Japan.
Takashi
T
Ujiie
Department of Urology, Sanai Hospital, Iwate, Japan.
Yutaka
Y
Nagane
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Kosaku
K
Nitta
Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Satoru
S
Miyano
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Ichiei
I
Narita
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Fumitake
F
Gejyo
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Hiroshi
H
Nihei
Department of Urology, Iwate Medical University, Iwate, Japan.
Tomoaki
T
Fujioka
Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo, Japan. yusuke@ims.u-tokyo.ac.jp.|Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. yusuke@ims.u-tokyo.ac.jp.
Yusuke
Y
Nakamura
D000328:Adult; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D019056:Receptors, Polymeric Immunoglobulin / Q000235:genetics* / Q000378:metabolism
D019056:Receptors, Polymeric Immunoglobulin