Cukovic-Cavka Silvija, Vermeire Severine, Hrstic Irena, Claessens Greet, Kolacek Sanja, Jakic-Razumovic Jasminka, Krznaric Zeljko, Grubelic Katja, Radic Davor, Misak Zrinjka, Jadresin Oleg, Rutgeerts Paul, Vucelic Boris
Division of Gastroenterology dDepartment of Pathology, University Hospital Rebro, Zagreb, Croatia.
Eur J Gastroenterol Hepatol. 2006 Aug;18(8):895-9. doi: 10.1097/00042737-200608000-00016.
Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with variations in localization and behaviour. Mutations in the NOD2/CARD15 gene on chromosome 16q have been implicated in the pathogenesis of the disease and three main sequence variants, all single nucleotide polymorphisms (SNPs), have been identified in North American and European populations.
As no data exist in the Croatian population, we consecutively collected a cohort of 136 CD patients and 91 healthy controls to determine the prevalence of NOD2/CARD15 mutations and their association with phenotypic expression of the disease. All patients and controls were genotyped for Arg702Trp (Hugot SNP8), Gly908Arg (Hugot SNP12), and Leu1007fsinsC (Hugot SNP13) and allele frequencies were compared between the Crohn's patients and controls. The correlation of NOD2/CARD15 genotypes with the phenotypic expression of Crohn's disease was further assessed by logistic regression analysis.
NOD2/CARD15 variants were found in 38/136 CD patients (27.9%) compared to 10/91 (10.9%) healthy controls (P = 0.0022). Allele frequencies in patients with CD were 13.97%, 4.4% and 11.76%, respectively, for SNP8, 12 and 13, compared to 5.49%, 1.12% and 4.40% in controls (P = 0.041, P = 0.162, P = 0.055). Six CD patients carried double mutations and, remarkably, we identified two homozygous mutants amongst the healthy control group. Surgery over the course of the disease and a younger age at onset of the disease were significantly more frequent in patients who were carriers of NOD2/CARD15 mutations.
This report on NOD2/CARD15 mutations in Croatian patients with CD demonstrates that this gene is also implicated in susceptibility to CD in the Croatian population. Phenotypic association showed a younger age at diagnosis and a higher need for surgery in patients carrying NOD2/CARD15 mutations. However, the prevalence is somewhat lower compared to other reports, likely due to a more prominent colonic inflammation.
克罗恩病（CD）是一种胃肠道慢性炎症性疾病，其病变部位和表现存在差异。16号染色体上NOD2/CARD15基因的突变与该疾病的发病机制有关，在北美和欧洲人群中已鉴定出三种主要的序列变异，均为单核苷酸多态性（SNP）。
由于克罗地亚人群中尚无相关数据，我们连续收集了136例CD患者和91例健康对照组成的队列，以确定NOD2/CARD15突变的患病率及其与疾病表型表达的关联。对所有患者和对照进行了Arg702Trp（Hugot SNP8）、Gly908Arg（Hugot SNP12）和Leu1007fsinsC（Hugot SNP13）的基因分型，并比较了克罗恩病患者和对照之间的等位基因频率。通过逻辑回归分析进一步评估NOD2/CARD15基因型与克罗恩病表型表达的相关性。
在136例CD患者中有38例（27.9%）发现了NOD2/CARD15变异，而在91例健康对照中有10例（10.9%）发现变异（P = 0.0022）。CD患者中SNP8、12和13的等位基因频率分别为13.97%、4.4%和11.76%，而对照中分别为5.49%、1.12%和4.40%（P = 0.041，P = 0.162，P = 0.055）。6例CD患者携带双重突变，值得注意的是，我们在健康对照组中鉴定出2例纯合突变体。在疾病过程中接受手术以及发病年龄较小在NOD2/CARD15突变携带者患者中更为常见。
这份关于克罗地亚CD患者中NOD2/CARD15突变的报告表明，该基因也与克罗地亚人群对CD的易感性有关。表型关联显示，携带NOD2/CARD15突变的患者诊断时年龄较小，手术需求更高。然而，与其他报告相比，患病率略低，可能是由于结肠炎症更为突出所致。
