日本人のUC多型(九州大学）：Nature Genetics最新online

Nature Genetics
Published online: 15 November 2009 | doi:10.1038/ng.482

A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population

1384人の潰瘍性大腸炎患者と3057人のコントロール
３つの関連多型を見出している

１）FCGR2A (rs1801274, P = 1.56 10-12
２）rs17085007（chromosome 13q12）, P = 6.64 10-8
３）SLC26A3 (rs2108225, P = 9.50 10-8).

九州大学は疫学（清原さん）が最近充実しているが、更に内科から炎症性腸疾患でこのような仕事が出たことは素晴らしい。この仕事はIBD研究を30年以上先頭に立って研究している飯田さんや松井さんの執念の産物のようにはたからは見える。本文を早く読んでみたい。

Kouichi Asano^1,2,3, Tomonaga Matsushita^1,2, Junji Umeno^1,2, Naoya Hosono¹, Atsushi Takahashi⁴, Takahisa Kawaguchi⁵, Takayuki Matsumoto², Toshiyuki Matsui⁶, Yoichi Kakuta⁷, Yoshitaka Kinouchi⁷, Tooru Shimosegawa⁷, Masayo Hosokawa⁸, Yoshiaki Arimura⁸, Yasuhisa Shinomura⁸, Yutaka Kiyohara³, Tatsuhiko Tsunoda⁵, Naoyuki Kamatani⁴, Mitsuo Iida², Yusuke Nakamura⁹ & Michiaki Kubo^1,2,3

Ulcerative colitis is one of the principal forms of inflammatory bowel disease with complex manifestations. Although previous studies have indicated that there is a genetic contribution to the pathogenesis of ulcerative colitis, the genes influencing susceptibility to the disease have not been fully determined. To identify genetic factors conferring risk of ulcerative colitis, here we conducted a two-stage genome-wide association study and subsequent replication study using 1,384 Japanese individuals with ulcerative colitis and 3,057 control subjects. In addition to the expected strong association with the major histocompatibility complex (MHC) region, we identified three new susceptibility loci: the immunoglobulin receptor gene FCGR2A (rs1801274, P = 1.56 10^-12), a locus on chromosome 13q12 (rs17085007, P = 6.64 10^-8) and the glycoprotein gene SLC26A3 (rs2108225, P = 9.50 10^-8). rs1801274 is a nonsynonymous SNP of FCGR2A that is reported to have a critical effect on receptor binding affinity for IgG and to be associated with other autoimmune diseases. Our findings provide insight into the molecular pathogenesis of ulcerative colitis.

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1. Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Yokohama Institute, Yokohama, Japan.
2. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
3. Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
4. Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Yokohama Institute, Japan.
5. Laboratory for Medical Informatics, Center for Genomic Medicine, RIKEN, Yokohama Institute, Japan.
6. Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
7. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
8. First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
9. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.