Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, Yokohama Institute, Yokohama, Japan.
Nat Genet. 2009 Dec;41(12):1325-9. doi: 10.1038/ng.482. Epub 2009 Nov 15.
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.
溃疡性结肠炎是炎症性肠病的主要形式之一，具有复杂的表现。尽管先前的研究表明溃疡性结肠炎的发病机制与遗传因素有关，但影响疾病易感性的基因尚未完全确定。为了确定溃疡性结肠炎的遗传风险因素，我们在这里对 1384 名溃疡性结肠炎患者和 3057 名对照者进行了两阶段全基因组关联研究和后续的复制研究。除了与主要组织相容性复合体（MHC）区域的预期强关联外，我们还确定了三个新的易感位点：免疫球蛋白受体基因 FCGR2A（rs1801274，P=1.56×10(-12)）、染色体 13q12 上的一个位点（rs17085007，P=6.64×10(-8)）和糖蛋白基因 SLC26A3（rs2108225，P=9.50×10(-8)）。rs1801274 是 FCGR2A 的非同义 SNP，据报道它对 IgG 受体结合亲和力有重要影响，并与其他自身免疫性疾病有关。我们的研究结果为溃疡性结肠炎的分子发病机制提供了新的见解。
