Zouali H, Lesage S, Merlin F, Cézard J-P, Colombel J-F, Belaiche J, Almer S, Tysk C, O'Morain C, Gassull M, Christensen S, Finkel Y, Modigliani R, Gower-Rousseau C, Macry J, Chamaillard M, Thomas G, Hugot J-P
Fondation Jean Dausset-CEPH, Paris, France.
Gut. 2003 Jan;52(1):71-4. doi: 10.1136/gut.52.1.71.
Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex genetic disorders. CARD15/NOD2, a member of the Ced4 superfamily which includes Apaf-1 and CARD4/NOD1, has recently been associated with genetic predisposition to CD but additional genetic factors remain to be identified. Because CARD4/NOD1 shares many structural and functional similarities with CARD15, we tested its putative role in IBD.
The 11 exons of CARD4 were screened for the presence of variants in 63 unrelated IBD patients. The only non-private genetic variation encoding for a substitution in the peptidic chain was genotyped in 381 IBD families (235 CD, 58 UC, 81 mixed, and seven indeterminate colitis families) using a polymerase chain reaction-restriction fragment length polymorphism procedure. Genotyping data were analysed by the transmission disequilibrium test.
Five of nine sequence variations identified in the coding sequence of the gene encoded for non-conservative changes (E266K, D372N, R705Q, T787M, and T787K). Four were present in only one family. The remaining variant (E266K), which exhibited an allele frequency of 0.28, was not associated with CD, UC, or IBD. Furthermore, IBD patients carrying sequence variations in their CARD4 gene had a similar phenotype to those with a normal sequence.
Our results suggest that CARD4 does not play a major role in genetic susceptibility to IBD.
炎症性肠病（IBD），包括克罗恩病（CD）和溃疡性结肠炎（UC），是复杂的遗传性疾病。CARD15/NOD2是Ced4超家族成员，该超家族包括Apaf-1和CARD4/NOD1，最近已发现其与CD的遗传易感性相关，但其他遗传因素仍有待确定。由于CARD4/NOD1与CARD15在结构和功能上有许多相似之处，我们检测了其在IBD中的假定作用。
对63例无亲缘关系的IBD患者的CARD4基因的11个外显子进行变异筛查。使用聚合酶链反应-限制性片段长度多态性方法，对381个IBD家系（235个CD家系、58个UC家系、81个混合型家系和7个不确定性结肠炎家系）中唯一编码肽链替代的非私有遗传变异进行基因分型。通过传递不平衡检验分析基因分型数据。
在该基因编码序列中鉴定出的9个序列变异中有5个编码非保守性改变（E266K、D372N、R705Q、T787M和T787K）。其中4个仅在1个家系中出现。其余变异（E266K）的等位基因频率为0.28，与CD、UC或IBD均无关联。此外，CARD4基因存在序列变异的IBD患者与序列正常的患者具有相似的表型。
我们的结果表明，CARD4在IBD的遗传易感性中不发挥主要作用。
