3p21 位点的变异既影响成人炎症性肠病患者的易感性，也影响其表型，也影响早发性炎症性肠病患者的易感性和表型。

Variants at the 3p21 locus influence susceptibility and phenotype both in adults and early-onset patients with inflammatory bowel disease.

机构信息

Division of Gastroenterology & Endoscopy, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy.

出版信息

Inflamm Bowel Dis. 2010 Jul;16(7):1108-17. doi: 10.1002/ibd.21176.

DOI:10.1002/ibd.21176

PMID:20024904

Abstract

BACKGROUND

To date, a number of high-profile studies have yielded over 50 inflammatory bowel disease (IBD) disease genes/loci. The polymorphisms rs9858542 (BSN) and rs3197999 (MST1), on 3p21 locus, have been found associated with susceptibility to IBD. We aimed to replicate these associations in adult and early-onset cohorts of IBD Italian patients, by analyzing also potential gene-gene interactions with variants in NOD2/CARD15, IL23R, ATG16L1, and IRGM genes, and investigating genotype-phenotype correlation.

METHODS

In all, 1808 patients with IBD, 855 with Crohn's disease (CD) and 953 with ulcerative colitis (UC), including 539 patients with their initial diagnosis <19 years of age, and 651 controls were analyzed for SNPs rs9858542 and rs3197999.

RESULTS

BSN and MST1 were significantly associated with either CD (P(rs9858542) 2.5 x 10(-7); P(rs3197999) 3.9 x 10(-7)), and UC (P(rs9858542) = 3.1 x 10(-4); P(rs3197999) = 8 x 10(-4)). Prevalence of these variants was significantly increased in both adult and early-onset IBD patients. After stepwise logistic regression, the 2 variants were associated in adult UC with distal colitis (P(rs9858542) = 0.013, odds ratio [OR] = 2.04, 95% confidence interval [CI] = 1.16-3.59; P(rs3197999) = 0.018, OR 1.9, 95% CI 1.2-3.3), while the rs3197999 variant was inversely associated with occurrence of extraintestinal manifestations in adult CD(P = 0.017, OR 0.6, 95% CI 0.4-0.9).

CONCLUSIONS

We confirmed the association of BSN and MST1 with IBD susceptibility, either in the adult or the early-onset cohorts. These variants appeared to influence either the distal location of the disease in the UC cohort and extraintestinal manifestations in CD patients.

摘要

背景

迄今为止，多项备受瞩目的研究已经发现了 50 多个炎症性肠病（IBD）疾病基因/位点。3p21 位点上的 rs9858542（BSN）和 rs3197999（MST1）多态性与 IBD 的易感性有关。我们旨在通过分析 NOD2/CARD15、IL23R、ATG16L1 和 IRGM 基因中的变异与潜在的基因-基因相互作用，并研究基因型-表型相关性，在意大利成年和早发性 IBD 患者的队列中复制这些关联。

方法

共分析了 1808 例 IBD 患者，855 例克罗恩病（CD）和 953 例溃疡性结肠炎（UC），其中 539 例患者的初始诊断年龄<19 岁，651 例为对照，分析了 rs9858542 和 rs3197999 的单核苷酸多态性。

结果

BSN 和 MST1 与 CD（P(rs9858542) 2.5 x 10(-7)；P(rs3197999) 3.9 x 10(-7)）和 UC（P(rs9858542) = 3.1 x 10(-4)；P(rs3197999) = 8 x 10(-4)）显著相关。这些变体在成年和早发性 IBD 患者中的患病率均显著增加。经过逐步逻辑回归，在成年 UC 中，这两个变体与远端结肠炎相关（P(rs9858542) = 0.013，优势比[OR] = 2.04，95%置信区间[CI] = 1.16-3.59；P(rs3197999) = 0.018，OR 1.9，95% CI 1.2-3.3），而 rs3197999 变体与成年 CD 中肠外表现的发生呈负相关（P = 0.017，OR 0.6，95% CI 0.4-0.9）。