Heliö T, Halme L, Lappalainen M, Fodstad H, Paavola-Sakki P, Turunen U, Färkkilä M, Krusius T, Kontula K
Department of Medicine, Helsinki University Hospital, Helsinki, Finland.
Gut. 2003 Apr;52(4):558-62. doi: 10.1136/gut.52.4.558.
Variants of the caspase activating recruitment domain 15/nucleotide oligomerisation domain 2 (CARD15/NOD2) gene have been associated with susceptibility to Crohn's disease (CD).
Our aim was to evaluate the allele frequencies of the CARD15 variants R702W, G908R, and 1007fs in Finnish inflammatory bowel disease (IBD) patients and to search for possible associations between CARD15 variants and occurrence of familial forms of IBD or complicated forms of CD.
We investigated 198 sporadic CD patients, 46 probands with familial CD, 27 CD probands from mixed IBD families, 99 unrelated patients with ulcerative colitis (UC), and 300 control individuals for the occurrence of the CARD15 gene variants R702W, G908R, and 1007fs.
In CD patients, the allele frequencies for the rare variants of these polymorphisms were 3.3%, 0.6%, and 4.8% (total 8.7%), and the corresponding frequencies in healthy controls were 1.8%, 0%, and 1.7% (total 3.5%) (8.7% v 3.5%; p<0.01). In UC patients allele frequencies were comparable with those in controls. The frequency of the 1007fs polymorphism variant allele was significantly higher among all CD patients than in controls (4.8% v 1.7%; p<0.01) but there was no significant difference in allele frequencies between the CD and UC groups. The 1007fs allele frequency was higher in familial CD than in non-familial cases with CD (10.9% v 3.5%; p<0.01). There were no significant differences in the allele frequencies of the R702W and G908R polymorphisms between CD patients, UC patients, and controls. We found that 15.5% of CD patients, 9.1% of UC patients, and 6.7% of controls carried at least one of the CARD15 variants. In CD patients carrying at least one of the three NOD2 variants, the ileum was affected more often than in non-carrier CD patients (90% v 73%; p<0.05), they had stricturing or penetrating disease more often than non-carriers (88% v 56%; p<0.01), and they had an increased need for bowel surgery.
The frequency of NOD2 gene variants was lower in genetically homogenous Finns than in other populations. The 1007fs variant was associated with CD. The occurrence of CARD15 variants predicted ileal location as well as stricturing and penetrating forms of CD.
胱天蛋白酶激活募集结构域15/核苷酸寡聚化结构域2（CARD15/NOD2）基因变异与克罗恩病（CD）易感性相关。
我们的目的是评估芬兰炎性肠病（IBD）患者中CARD15变异体R702W、G908R和1007fs的等位基因频率，并寻找CARD15变异体与IBD家族形式或CD复杂形式发生之间的可能关联。
我们调查了198例散发性CD患者、46例家族性CD先证者、27例来自混合IBD家族的CD先证者、99例非相关性溃疡性结肠炎（UC）患者以及300例对照个体，以检测CARD15基因变异体R702W、G908R和1007fs的发生情况。
在CD患者中，这些多态性罕见变异体的等位基因频率分别为3.3%、0.6%和4.8%（总计8.7%），而健康对照中的相应频率分别为1.8%、0%和1.7%（总计3.5%）（8.7%对3.5%；p<0.01）。UC患者的等位基因频率与对照相当。1007fs多态性变异等位基因在所有CD患者中的频率显著高于对照（4.8%对1.7%；p<0.01），但CD组和UC组之间的等位基因频率无显著差异。1007fs等位基因频率在家族性CD中高于非家族性CD病例（10.9%对3.5%；p<0.01）。R702W和G908R多态性的等位基因频率在CD患者、UC患者和对照之间无显著差异。我们发现15.5%的CD患者、9.1%的UC患者和6.7%的对照携带至少一种CARD15变异体。在携带至少一种三种NOD2变异体的CD患者中，回肠受累比非携带者CD患者更常见（90%对73%；p<0.05），他们比非携带者更常发生狭窄或穿透性疾病（88%对56%；p<0.01），并且他们对肠道手术的需求增加。
在基因同质的芬兰人中，NOD2基因变异体的频率低于其他人群。1007fs变异体与CD相关。CARD15变异体的发生可预测CD的回肠部位以及狭窄和穿透形式。
