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

作者：Asano Kouichi; Matsushita Tomonaga; Umeno Junji; Hosono Naoya; Takahashi Atsushi; Kawaguchi Takahisa; Matsumoto Takayuki; Matsui Toshiyuki; Kakuta Yoichi; Kinouchi Yoshitaka; Shimosegawa Tooru; Hosokawa Masayo; Arimura Yoshiaki; Shinomura Yasuhisa; Kiyohara Yutaka; Tsunoda Tatsuhiko; Kamatani Naoyuki; Iida Mitsuo; Nakamura Yusuke; Kubo Michiaki^*

来源：Nature Genetics, 2009, 41(12): 1325-U92.

DOI：10.1038/ng.482

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 x 10(-12)), a locus on chromosome 13q12 (rs17085007, P = 6.64 x 10(-8)) and the glycoprotein gene SLC26A3 (rs2108225, P = 9.50 x 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.

• 出版日期2009-12
• 单位河北医科大学