Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease
Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease
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DOI：
10.1053/gast.2002.35393
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发表时间：
2002-09-01
期刊：
影响因子：
29.4
通讯作者：
Yang, HY
中科院分区：
文献类型：
--
作者：
Abreu, MT;Taylor, KD;Yang, HY
背景和目标：克罗恩病（CD）的临床表现多种多样，从纤维狭窄性小肠疾病到结肠为主的炎症。这些差异可能代表遗传、免疫和微生物的异质性。最近已经描述了CID中的NOD 2基因突变，并且可能改变先天免疫应答。我们假设NOD 2突变可能与CID的不同表型表达相关。研究方法：两个队列的连续确定的患者提到炎症性肠病中心（n = 142收集1993年和1996年之间，n = 59收集：1999年和200：1）进行基因分型的3个单核苷酸变异的NOD 2-R675 W，G881 R，和3020 insC-和表型的疾病行为，疾病的位置，和血清免疫标记。结果如下：单变量分析显示，CID相关的NOD 2变异与每个队列中的纤维狭窄疾病显著相关（分别为P = 0.049和P = 0.002）。当两个队列一起分析时，NOD 2变体与纤维狭窄疾病之间的关联更显著（P = 0.001）。这些关系在犹太人和非犹太人身上都能观察到。46%的纤维狭窄性疾病患者携带至少一种这些等位基因，相比之下，只有23.5%的非纤维狭窄性疾病患者携带这些等位基因（比值比，2.8; 95%置信区间，16-5.2）。多变量和条件分析显示NOD 2等位基因变异与纤维狭窄性疾病之间存在主要相关性，但与小肠疾病无关。结论：在CID患者和NOD 2变体的基因型/表型相关性的描述中，数据表明该基因的变异有助于小肠纤维狭窄CID的发生。
Background & Aims: The clinical manifestations of Crohn's disease (CD) are diverse, ranging from fibrostenosing small-bowel disease to colon-predominant inflammation. These distinctions may represent genetic, immunologic, and microbial heterogeneity. NOD2 gene mutations in CID have been described recently and may alter innate immune responses. We hypothesized that NOD2 mutations may be associated with distinct phenotypic expressions of CID. Methods: Two cohorts of consecutively identified patients referred to an inflammatory bowel disease center (n = 142 collected between 1993 and 1996; n = 59 collected between :1999 and 200:1) were genotyped for 3 single nucleotide variants of NOD2-R675W, G881R, and 3020insC-and phenotyped for disease behavior, disease location, and serum immune markers. Results: Univariate analysis showed that CID-associated NOD2 variants were significantly associated with fibrostenosing disease in each cohort (P = 0.049 and P = 0.002, respectively). When both cohorts were analyzed together, the association between NOD2 variants and fibrostenosing disease was more significant (P = 0.001). These relationships were observed in both Jews and non-Jews. Forty-six percent of patients with fibrostenosing disease carried at least 1 of these alleles, compared with only 23.5% of patients without fibrostenosing disease (odds ratio, 2.8; 95% confidence interval, 16-5.2). Multivariate and conditioning analyses showed a primary association between NOD2 allelic variants and fibrostenosing disease, but not with small-bowel disease. Conclusions: In this description of a genotype/phenotype correlation in CID patients and NOD2 variants, data suggest that variation in this gene contributes to the occurrence of fibrostenotic CID of the small bowel.