Ferraris Alessandro, Torres Barbara, Knafelz Daniela, Barabino Arrigo, Lionetti Paolo, de Angelis Gian Luigi, Iacono Giuseppe, Papadatou Bronislava, D'Amato Giovanna, Di Ciommo Vincenzo, Dallapiccola Bruno, Castro Massimo
IRCCS CSS Hospital, San Giovanni Rotondo, and CSS-Mendel Institute, Rome, Italy.
Inflamm Bowel Dis. 2006 May;12(5):355-61. doi: 10.1097/01.MIB.0000217338.23065.58.
Inflammatory bowel disease (IBD) has been associated with several polymorphisms in genes likely involved in innate immune responses and integrity of epithelial mucosal barrier. A major role in adult Crohn's disease (CD) has been defined for 3 polymorphisms in the CARD15 gene, whereas variants in the SLC22A4, SLC22A5, and DLG5 genes could have a minor contribution to IBD susceptibility.
We analyzed a panel of 6 polymorphisms within these genes in 227 Italian early-onset IBD patients (134 CD, 93 ulcerative colitis [UC]; age at diagnosis <or=18 years) and 166 unaffected control subjects.
Each CARD15 variant was found to be independently associated with CD. After the genotypes at the 3 polymorphisms were combined, 37.3% patients carried at least 1 variant compared with 9.2% control subjects (odds ratio, 5.87; 95% CI 3.11-11.1; P < 0.001). The combined frequency of CARD15 variants was also higher in UC children compared with control subjects (14% vs 9.2%), but this difference was not significant. However, CARD15 variants were associated with earlier onset of UC, and the mutation rate was significantly higher in UC patients with onset at or before 6 years of age compared with control subjects (27.6% vs 9.2%) (odds ratio = 3.76; 95% CI 1.42-9.94; P = 0.01). CARD15 variants also were associated with ileal CD involvement and a higher rate of extraintestinal manifestations in UC. Allele and genotype frequencies at SLC22A and DLG5 polymorphisms were not significantly different between cases and controls.
Our results demonstrate that in the Italian population, the major CARD15 polymorphisms are associated with susceptibility to early-onset CD and with ileal involvement and suggest a previously unreported association with very early-onset, severe UC.
炎症性肠病（IBD）与可能参与先天免疫反应及上皮黏膜屏障完整性的多个基因多态性有关。CARD15基因中的3种多态性在成人克罗恩病（CD）中起主要作用，而SLC22A4、SLC22A5和DLG5基因中的变异对IBD易感性可能有较小影响。
我们分析了227例意大利早发型IBD患者（134例CD、93例溃疡性结肠炎[UC]；诊断时年龄≤18岁）和166例未受影响对照者中这些基因的6种多态性。
发现每种CARD15变异均与CD独立相关。在将3种多态性的基因型合并后，37.3%的患者携带至少1种变异，而对照者为9.2%（比值比，5.87；95%可信区间3.11 - 11.1；P < 0.001）。与对照者相比，UC儿童中CARD15变异的合并频率也更高（14%对9.2%），但这种差异不显著。然而，CARD15变异与UC的发病较早相关，与对照者相比，6岁及6岁以前发病的UC患者的突变率显著更高（27.6%对9.2%）（比值比 = 3.76；95%可信区间1.42 - 9.94；P = 0.01）。CARD15变异还与回肠CD累及以及UC中更高的肠外表现发生率相关。SLC22A和DLG5多态性的等位基因和基因型频率在病例组和对照组之间无显著差异。
我们的结果表明，在意大利人群中，主要的CARD15多态性与早发型CD易感性以及回肠累及相关，并提示与极早发型、严重UC存在此前未报道的关联。
