Variants of CARD 15 are associated with an aggressive clinical course of Crohn's disease -: An IG-IBD study
Variants of CARD 15 are associated with an aggressive clinical course of Crohn's disease -: An IG-IBD study
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DOI：
10.1111/j.1572-0241.2005.40705.x
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发表时间：
2005-01-01
影响因子：
9.8
通讯作者：
Andriulli, A
中科院分区：
文献类型：
--
作者：
Annese, V;Lombardi, G;Andriulli, A
背景：CARD 15基因的三种主要变异体赋予克罗恩病（CD）的易感性。这些变异是否与疾病的特定临床特征相关正在评估中。目的：我们在一个大的炎症性肠病（IBD）患者及其未受影响的亲属队列中研究了CARD 15变异与特定临床特征的可能关联，包括抗酿酒酵母抗体（ASCA）和抗神经营养素胞浆抗体（ANCA）的发生。研究了316例CD患者（156例阳性家族史），408例溃疡性结肠炎（UC）患者（206例阳性家族史），588例未受影响的亲属和205例无关的健康对照（HC）。研究了CARD 15基因的单核苷酸多态性（SNP）R702 W、G908 R和L1007 finsC，并将其与诊断时的年龄、性别、家族史、定位、肠外表现、既往切除手术、狭窄/瘘管形成模式、ANCA和ASCA.RESULTS：与HC相比，CD中所有三种变体的频率显著增加：R702 W为8.7%对4.1%（p < 0.006），G908 R为7.3%对2.7%（p < 0.002），L1007 finsC为9.3%对0.7%（p < 0.00001）。在CD、UC和HC中分别有38.2%（p < 0.0001，与HC相比）、13.7%（NS）和15.1%发现至少一个危险等位基因。与HC（0.7%）相比，家族性CD（9.5%; p < 0.00001）和散发性CD（9%; p < 0.00001）的未受影响亲属中的L1007 finsC风险等位基因也显著增加。16名健康的亲属，携带两个危险等位基因，在5-8年的随访后无症状。至少一种变异的CD携带者更年轻（p = 0.03），更可能有回肠定位（p = 0.0001），狭窄模式（p = 0.01），既往切除手术（p = 0.0001）和ASCA（p = 0.0001）。家族性和散发性CD病例之间的SNPs频率无差异were found.CONCLUSION：在我们的人群中，家族性和散发性CD患者携带至少一个CARD 15主要变异体，具有侵袭性临床病程。
BACKGROUND: Three major variants of the CARD15 gene confer susceptibility to Crohn's disease (CD). Whether or not these variants correlate with specific clinical features of the disease is under evaluation.AIM: We investigated the possible association of CARD15 variants with specific clinical characteristics, including the occurrence of anti-Saccharomyces cerevisiae antibodies (ASCA) and antineutrophil cytoplasmic antibodies (ANCA), in a large cohort of inflammatory bowel disease (IBD) patients and their unaffected relatives.METHODS: Three hundred and sixteen CD patients (156 with positive family history), 408 ulcerative colitis (UC) patients (206 with positive family history), 588 unaffected relatives, and 205 unrelated healthy controls (HC) were studied. Single nucleotide polymorphisms (SNPs) R702W, G908R, and L1007finsC of the CARD15 gene were investigated and correlated to age at diagnosis, gender, family history, localization, extraintestinal manifestations, previous resective surgery, stenosing/fistulizing pattern, ANCA, and ASCA.RESULTS: Compared to HC, the frequencies of all three variants in CD were significantly increased: 8.7% versus 4.1% for R702W (p < 0.006), 7.3% versus 2.7% for G908R (p < 0.002), 9.3% versus 0.7% for L1007finsC (p < 0.00001). At least one risk allele was found in 38.2% (p < 0.0001, compared to HC), 13.7% (NS), and 15.1% of CD, UC, and HC, respectively. The L1007finsC risk allele was also significantly increased in unaffected relatives of familial (9.5%; p < 0.00001), and sporadic CD (9%; p < 0.00001), compared to HC (0.7%). Sixteen healthy relatives, carriers of two risk alleles, were asymptomatic after 5-8 yr of follow-up. CD carriers of at least one variant were younger (p = 0.03), more likely to have ileal localization (p = 0.0001), stenosing pattern (p = 0.01), previous resective surgery (p = 0.0001), and presence of ASCA (p = 0.0001). No difference in SNPs frequency between familial and sporadic cases of CD was found.CONCLUSION: In our population, both familial and sporadic CD patients carrying at least one major variant of CARD15 had an aggressive clinical course.