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Single-nucleotide polymorphisms in the class II region of the major histocompatibility complex in Japanese patients with immunoglobulin A nephropathy |
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| Authors: | Akiyama Fumihiro Tanaka Toshihiro Yamada Ryo Ohnishi Yozo Tsunoda Tatsuhiko Maeda Shiro Takei Takashi Obara Wataru Ito Kyoko Honda Kazuho Uchida Keiko Tsuchiya Ken Nitta Kosaku Yumura Wako Nihei Hiroshi Ujiie Takashi Nagane Yutaka Miyano Satoru Suzuki Yasushi Fujioka Tomoaki Narita Ichiei Gejyo Fumitake Nakamura Yusuke |
| Affiliation: | (1) Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo, Japan, JP;(2) Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan, JP;(3) Laboratory for Cardiovascular Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan, JP;(4) Laboratory for Rheumatic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan, JP;(5) Laboratory for Medical Informatics, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan, JP;(6) Laboratory for Diabetic Nephropathy, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan, JP;(7) Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan, JP;(8) Department of Urology, Iwate Prefectural Ofunato Hospital, Iwate, Japan, JP;(9) Department of Urology, Sanai Hospital, Iwate, Japan, JP;(10) Department of Urology, Iwate Medical University, Iwate, Japan, JP;(11) 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, JP |
| Abstract: | Immunoglobulin A nephropathy (IgAN) is a form of chronic glomerulonephritis of unknown etiology and pathogenesis. Immunogenetic studies have not conclusively indicated that human leukocyte antigen (HLA) is involved. As a first step in investigating a possible relationship between HLA class II genes and IgAN, we analyzed the extent of linkage disequilibrium (LD) in this region of chromosome 6p21.3 in a Japanese test population and found extended LD blocks within the class II locus. We designed a case-control association study of single-nucleotide polymorphisms (SNPs) in each of those LD blocks, and determined that SNPs located in the HLA-DRA gene were significantly associated with an increased risk of IgAN (P = 0.000001, odds ratio = 1.91 [95% confidence interval 1.46–2.49]); SNPs in other LD blocks were not. Our data imply that some haplotype of the HLA-DRA locus has an important role in the development of IgAN in Japanese patients. Received: May 28, 2002 / Accepted: July 4, 2002 |
| Keywords: | Single-nucleotide polymorphism IgA nephropathy Linkage disequilibrium HLA class II HLA-DRA |
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