Association of a single-nucleotide polymorphism in the immunoglobulin mu-binding protein 2 gene with immunoglobulin A nephropathy.
Immunoglobulin A (IgA) nephropathy is the most common form of primary glomerulonephritis worldwide. The pathogenesis of IgA nephropathy is unknown, but it is certain that some genetic factors are involved in susceptibility to the disease. Employing a large-scale, case-control association study using gene-based single-nucleotide polymorphism (SNP) markers, we previously reported four candidate genes. We report here an additional significant association between IgA nephropathy and an SNP located in the gene encoding immunoglobulin micro-binding protein 2 (IGHMBP2) at chromosome 11q13.2-q13.4. The association (chi2 =17.1, p = 0.00003; odds ratio of 1.85 with 95% confidence interval of 1.39-2.50 in a dominant association model) was found using DNA from 465 affected individuals and 634 controls. The SNP (G34448A) caused an amino acid substitution from glutamine to lysine (E928K). As the gene product is involved in immunoglobulin-class switching and patients with the A allele revealed higher serum levels of IgA (p = 0.048), the amino acid change might influence a class switch to increase serum IgA levels, resulting in a higher risk of IgA nephropathy.
Ohtsubo
Shigeru
S
Human Genome Center, The Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.|Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Iida
Aritoshi
A
Laboratory for Genotyping, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
Nitta
Kosaku
K
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Tanaka
Toshihiro
T
Laboratory for Cardiovascular Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
Yamada
Ryo
R
Laboratory for Rheumatic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
Ohnishi
Yozo
Y
Laboratory for Cardiovascular Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
Maeda
Shiro
S
Laboratory for Diabetic Nephropathy, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
Tsunoda
Tatsuhiko
T
Laboratory for Medical Informatics, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
Takei
Takashi
T
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Obara
Wataru
W
Department of Urology, Iwate Medical University, Iwate, Japan.
Akiyama
Fumihiro
F
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Ito
Kyoko
K
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Honda
Kazuho
K
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Uchida
Keiko
K
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Tsuchiya
Ken
K
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Yumura
Wako
W
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Ujiie
Takashi
T
Department of Urology, Iwate Prefectural Ofunato Hospital, Iwate, Japan.
Nagane
Yutaka
Y
Department of Urology, Sanai Hospital, Iwate, Japan.
Miyano
Satoru
S
Human Genome Center, The Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
Suzuki
Yasushi
Y
Department of Urology, Iwate Medical University, Iwate, Japan.
Narita
Ichiei
I
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Gejyo
Fumitake
F
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Fujioka
Tomoaki
T
Department of Urology, Iwate Medical University, Iwate, Japan.
Nihei
Hiroshi
H
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Nakamura
Yusuke
Y
Human Genome Center, The Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan. yusuke@ims.u-tokyo.ac.jp.
D000328:Adult; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005922:Glomerulonephritis, IGA / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C489892:IGHMBP2 protein, human; D014157:Transcription Factors