A genome-wide association study identifies IL23R as an inflammatory bowel disease gene
A genome-wide association study identifies IL23R as an inflammatory bowel disease gene
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DOI：
10.1126/science.1135245
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发表时间：
2006-12-01
期刊：
影响因子：
56.9
通讯作者：
Cho, Judy H.
中科院分区：
文献类型：
--
作者：
Duerr, Richard H.;Taylor, Kent D.;Cho, Judy H.
炎症性肠病克罗恩病和溃疡性结肠炎是常见的慢性疾病，会引起腹痛、腹泻和胃肠道出血。为了确定可能导致这些疾病的遗传因素，我们进行了全基因组关联研究。我们发现克罗恩病与染色体1p31上的IL23R基因之间存在高度显著的关联，该基因编码促炎细胞因子白细胞介素-23受体的一个亚基。一种不常见的编码变体（rs11209026, c. 1142G> A, p. Arg381Gln）对克罗恩病具有很强的保护作用，其他非编码IL23R变体独立相关。重复性研究证实，在克罗恩病或溃疡性结肠炎患者的独立队列中，IL23R存在关联。这些结果和先前关于IL-23促炎作用的研究优先考虑将该信号通路作为炎症性肠病的治疗靶点。
The inflammatory bowel diseases Crohn's disease and ulcerative colitis are common, chronic disorders that cause abdominal pain, diarrhea, and gastrointestinal bleeding. To identify genetic factors that might contribute to these disorders, we performed a genome-wide association study. We found a highly significant association between Crohn's disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the proinflammatory cytokine interleukin-23. An uncommon coding variant (rs11209026, c. 1142G> A, p. Arg381Gln) confers strong protection against Crohn's disease, and additional noncoding IL23R variants are independently associated. Replication studies confirmed IL23R associations in independent cohorts of patients with Crohn's disease or ulcerative colitis. These results and previous studies on the proinflammatory role of IL-23 prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease.