Seiderer Julia, Schnitzler Fabian, Brand Stephan, Staudinger Tanja, Pfennig Simone, Herrmann Karin, Hofbauer Katrin, Dambacher Julia, Tillack Cornelia, Sackmann Michael, Göke Burkhard, Lohse Peter, Ochsenkühn Thomas
Department of Internal Medicine II, University of Munich, Germany.
Scand J Gastroenterol. 2006 Dec;41(12):1421-32. doi: 10.1080/00365520600703900.
The identification of CARD15 as a susceptibility gene for Crohn's disease (CD) offers new possibilities for patient classification and risk assessment. The purpose of this study was to carry out a CARD15 sequence analysis in a large single-center IBD cohort and to investigate the impact of different genotypes on disease phenotypes.
A total of 445 unrelated patients with IBD (68.1% CD, 28.5% ulcerative colitis (UC), 3.4% indeterminate colitis (IC)) were included in the study. Clinical data were recorded by detailed questionnaire and analysis of the charts. CARD15 variants (R702W, G908R, 1007fs (frameshift)) were identified by DNA sequence analysis.
CARD15 variants were found in 142 inflammatory bowel disease (IBD) patients (31.9%) including 120 CD patients (39.6%). In CD, the presence of two CARD15 variants was associated with ileal disease (p=0.008 versus wild-type (wt); OR 4.04; 95% CI 1.36-11.96) and a fibrostenotic phenotype (p=0.002 versus wt; OR 5.47; 95% CI 1.61-18.58). Subgroup analysis of 19 patients (4.3%) homozygous for the CARD15 variant 1007fs (3020ins C) revealed an association with onset of CD at an early age (p=0.014 versus wt), ileal involvement (p=0.001), and intestinal stenoses in all patients (p=0.001) frequently requiring surgery (73.7%; p=0.093). Of these patients 78.6% developed re-stenoses after surgical resection; 52.6% of the homozygotes were diagnosed as having entero-enteral fistulas.
Patients homozygous for the 1007fs mutation had an early disease onset with long-segment ileal stenoses and entero-enteral fistulas. They frequently needed surgical intervention and had a high risk of re-stenosis. Genotyping therefore appears to be an important diagnostic tool in identifying severely affected patients requiring individualized treatment strategies at an early stage of the disease.
CARD15被鉴定为克罗恩病（CD）的易感性基因，这为患者分类和风险评估提供了新的可能性。本研究的目的是在一个大型单中心炎症性肠病（IBD）队列中进行CARD15序列分析，并研究不同基因型对疾病表型的影响。
本研究共纳入445例无亲缘关系的IBD患者（68.1%为CD，28.5%为溃疡性结肠炎（UC），3.4%为不确定性结肠炎（IC））。通过详细问卷和病历分析记录临床数据。通过DNA序列分析鉴定CARD15变异体（R702W、G908R、1007fs（移码））。
在142例炎症性肠病（IBD）患者（31.9%）中发现CARD15变异体，其中包括120例CD患者（39.6%）。在CD中，两个CARD15变异体的存在与回肠疾病相关（与野生型（wt）相比，p=0.008；OR 4.04；95%CI 1.36-11.96）和纤维狭窄表型（与wt相比，p=0.002；OR 5.47；95%CI 1.61-18.58）。对19例（4.3%）CARD15变异体1007fs（3020ins C）纯合子患者的亚组分析显示，其与CD早期发病相关（与wt相比，p=0.014）、回肠受累（p=0.001）以及所有患者的肠道狭窄相关（p=0.001），这些患者经常需要手术（73.7%；p=0.093）。在这些患者中，78.6%在手术切除后出现再狭窄；52.6%的纯合子被诊断为肠-肠瘘。
1007fs突变纯合子患者疾病发病早，有长段回肠狭窄和肠-肠瘘。他们经常需要手术干预，且再狭窄风险高。因此，基因分型似乎是一种重要的诊断工具，可用于识别在疾病早期需要个体化治疗策略的严重受累患者。
