Laghi L, Costa S, Saibeni S, Bianchi P, Omodei P, Carrara A, Spina L, Contessini Avesani E, Vecchi M, De Franchis R, Malesci A
Division of Gastroenterology, Istituto Clinico Humanitas, Rozzano, Italy.
Aliment Pharmacol Ther. 2005 Sep 15;22(6):557-64. doi: 10.1111/j.1365-2036.2005.02629.x.
It is controversial whether CARD15 variants are truly associated with a more severe form of Crohn's disease. The relative role of CARD15 genotype and smoking in Crohn's disease progression is also debated.
To investigate the association between CARD15 variants and history of resective surgery in patients with Crohn's ileal disease, taking into account smoking as a possible confounding factor.
We originally assessed CARD15 genotype in 239 north Italian Crohn's disease patients (mean follow-up: 10.1 +/- 8.1 years). We then focused on 193 patients with proven ileal involvement, 70 of whom (36.3%) carried CARD15-mutated alleles (G908R, R702W, L1007fs).
Carriage of CARD15 variants was positively associated with family history and ileal-only disease and negatively associated with uncomplicated behaviour at maximal follow-up (P < 0.05). Ileal resection was the only variable independently associated with CARD15 variants at multivariate analysis (OR 3.8; 95% CI 1.6-9.2; P = 0.003). Kaplan-Meier analysis showed that ileal resection was favoured both by CARD15 variant-carriage (P = 0.01) and by smoking (P = 0.05), but smoking did not affect progression to surgery in variant carriers (P = 0.31). Thirteen of 14 (93%) patients being resection-free at 15-year follow-up, had CARD15 wild-type genotype (P = 0.01), whereas only seven (50%) had never smoked (P = 1.0).
In summary, CARD15 variant-associated Crohn's ileitis is virtually committed to stricturing and/or penetrating disease and, eventually, to resective surgery. Smoking accelerates progression to surgery in patients with wild-type CARD15 genotype, but it seems to exert no additional effect in CARD15-variant carriers.
CARD15基因变异是否真的与更严重形式的克罗恩病相关存在争议。CARD15基因型和吸烟在克罗恩病进展中的相对作用也存在争议。
考虑吸烟作为可能的混杂因素，研究CARD15基因变异与克罗恩回肠疾病患者切除手术史之间的关联。
我们最初对239名意大利北部克罗恩病患者评估了CARD15基因型（平均随访时间：10.1±8.1年）。然后我们聚焦于193名经证实有回肠受累的患者，其中70名（36.3%）携带CARD15突变等位基因（G908R、R702W、L1007fs）。
携带CARD15基因变异与家族史和仅累及回肠的疾病呈正相关，与最大随访时的非复杂性病情呈负相关（P<0.05）。在多变量分析中，回肠切除术是与CARD15基因变异独立相关的唯一变量（比值比3.8；95%置信区间1.6 - 9.2；P = 0.003）。Kaplan-Meier分析表明，回肠切除术既受CARD15基因变异携带状态影响（P = 0.01），也受吸烟影响（P = 0.05），但吸烟对携带变异基因者的手术进展无影响（P = 0.31）。在15年随访时未接受切除术的14名患者中有13名（93%）具有CARD15野生型基因型（P = 0.），而只有7名（50%）从未吸烟（P = 1.0）。
总之，与CARD15基因变异相关的克罗恩回肠炎实际上会导致狭窄和/或穿透性疾病，并最终导致切除手术。吸烟会加速野生型CARD15基因型患者进展至手术，但对携带CARD15基因变异者似乎没有额外影响。
