Ernst Anja, Jacobsen Bent, Østergaard Mette, Okkels Henrik, Andersen Vibeke, Dagiliene Enrika, Pedersen Inge S, Thorsgaard Niels, Drewes Asbjørn M, Krarup Henrik B
Department of Clinical Biochemistry, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark.
Scand J Gastroenterol. 2007 Dec;42(12):1445-51. doi: 10.1080/00365520701427102.
Three CAspase Recruitment Domain (CARD15) mutations have shown to predispose to Crohn's disease in Caucasian populations. The aim of this study was to investigate the mutation frequency in patients with inflammatory bowel disease and in healthy controls in Denmark.
Genotyping of the three common CARD15 mutations was carried out on 388 patients with Crohn's disease, 565 patients with ulcerative colitis and 796 healthy controls using real-time PCR. Allele and genotype frequencies in the three groups were compared. A possible additive effect of smoking on CARD15 mutations was also examined.
Carrying at least one CARD15 mutation was significantly more common in patients with Crohn's disease compared with healthy controls (21% versus 10%; p <0.001). A gene-dosage effect was observed (ORadj.smoking 22.2; p <0.001 for carrying two CARD15 mutations versus ORadj.smoking 1.8; p=0.01 for carrying one CARD15 mutation). The 1007insC protein truncating mutation was the major contributing mutation. Ileal involvement was more common in Crohn's disease patients with CARD15 mutations as opposed to patients without CARD15 mutations (ORadj.smoking 3.6; p <0.001). Smoking was independently associated with Crohn's disease (OR 1.8; p <0.001), but no multiplicative effect of smoking on CARD15 genotypes was found.
In the Danish population, CARD15 mutations were found to be associated with Crohn's disease, hence supporting the hypothesis of a genetic component contributing to the disease. Further research for other genes possibly involved in Crohn's disease may result in the use of genetic testing for diagnosis or treatment of Crohn's disease in the future.
在白种人群中，三种胱天蛋白酶招募结构域（CARD15）突变已被证明易患克罗恩病。本研究的目的是调查丹麦炎性肠病患者和健康对照者中这些突变的频率。
采用实时聚合酶链反应（PCR）对388例克罗恩病患者、565例溃疡性结肠炎患者和796例健康对照者进行三种常见CARD15突变的基因分型。比较三组的等位基因和基因型频率。还研究了吸烟对CARD15突变可能的累加效应。
与健康对照者相比，携带至少一种CARD15突变在克罗恩病患者中更为常见（21%对10%；p<0.001）。观察到基因剂量效应（校正吸烟因素后，携带两种CARD15突变的比值比为22.2；p<0.001，而携带一种CARD15突变的校正吸烟因素后比值比为1.8；p=0.01）。1007insC蛋白截短突变是主要的致病突变。与无CARD15突变的克罗恩病患者相比，有CARD15突变的患者回肠受累更为常见（校正吸烟因素后比值比为3.6；p<0.001）。吸烟与克罗恩病独立相关（比值比为1.8；p<0.001），但未发现吸烟对CARD15基因型有倍增效应。
在丹麦人群中，发现CARD15突变与克罗恩病相关，因此支持了遗传因素导致该病的假说。对可能参与克罗恩病的其他基因进行进一步研究，可能会在未来将基因检测用于克罗恩病的诊断或治疗。
