title: Association of a single-nucleotide polymorphism in the immunoglobulin mu-binding protein 2 gene with immunoglobulin A nephropathy.
abstract: 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.
authors.affiliation: 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.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohtsubo
authors.affiliation: Laboratory for Genotyping, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
authors.forename: Aritoshi
authors.initials: A
authors.lastname: Iida
authors.affiliation: Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kosaku
authors.initials: K
authors.lastname: Nitta
authors.affiliation: Laboratory for Cardiovascular Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Laboratory for Rheumatic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamada
authors.affiliation: Laboratory for Cardiovascular Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
authors.forename: Yozo
authors.initials: Y
authors.lastname: Ohnishi
authors.affiliation: Laboratory for Diabetic Nephropathy, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Maeda
authors.affiliation: Laboratory for Medical Informatics, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.affiliation: Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takei
authors.affiliation: Department of Urology, Iwate Medical University, Iwate, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Obara
authors.affiliation: Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Akiyama
authors.affiliation: Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ito
authors.affiliation: Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kazuho
authors.initials: K
authors.lastname: Honda
authors.affiliation: Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Tsuchiya
authors.affiliation: Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Wako
authors.initials: W
authors.lastname: Yumura
authors.affiliation: Department of Urology, Iwate Prefectural Ofunato Hospital, Iwate, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ujiie
authors.affiliation: Department of Urology, Sanai Hospital, Iwate, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nagane
authors.affiliation: Human Genome Center, The Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyano
authors.affiliation: Department of Urology, Iwate Medical University, Iwate, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Ichiei
authors.initials: I
authors.lastname: Narita
authors.affiliation: Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Fumitake
authors.initials: F
authors.lastname: Gejyo
authors.affiliation: Department of Urology, Iwate Medical University, Iwate, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Fujioka
authors.affiliation: Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nihei
authors.affiliation: 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.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: 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*
chemical_list: D004268:DNA-Binding Proteins; C489892:IGHMBP2 protein, human; D014157:Transcription Factors