Université Paris Diderot, UMR843, Paris, France.
PLoS One. 2012;7(12):e52223. doi: 10.1371/journal.pone.0052223. Epub 2012 Dec 27.
BACKGROUND & AIMS: Recent studies reported a role for more than 70 genes or loci in the susceptibility to Crohn's disease (CD). However, the impact of these associations in clinical practice remains to be defined. The aim of the study was to analyse the relationship between genotypes and phenotypes for the main 53 CD-associated polymorphisms.
A cohort of 798 CD patients with a median follow up of 7 years was recruited by tertiary adult and paediatric gastroenterological centres. A detailed phenotypic description of the disease was recorded, including clinical presentation, response to treatments and complications. The participants were genotyped for 53 CD-associated variants previously reported in the literature and correlations with clinical sub-phenotypes were searched for. A replication cohort consisting of 722 CD patients was used to further explore the putative associations.
The NOD2 rare variants were associated with an earlier age at diagnosis (p = 0.0001) and an ileal involvement (OR = 2.25[1.49-3.41] and 2.77 [1.71-4.50] for rs2066844 and rs2066847, respectively). Colonic lesions were positively associated with the risk alleles of IL23R rs11209026 (OR = 2.25 [1.13-4.51]) and 6q21 rs7746082 (OR = 1.60 [1.10-2.34] and negatively associated with the risk alleles of IRGM rs13361189 (OR = 0.29 [0.11-0.74]) and DEFB1 rs11362 (OR = 0.50 [0.30-0.80]). The ATG16L1 and IRGM variants were associated with a non-inflammatory behaviour (OR = 1.75 [1.22-2.53] and OR = 1.50 [1.04-2.16] respectively). However, these associations lost significance after multiple testing corrections. The protective effect of the IRGM risk allele on colonic lesions was the only association replicated in the second cohort (p = 0.03).
It is not recommended to genotype the studied polymorphisms in routine practice.
最近的研究报告了 70 多个基因或基因座在克罗恩病（CD）易感性中的作用。然而，这些关联在临床实践中的影响仍有待确定。本研究的目的是分析主要 53 个 CD 相关多态性的基因型与表型之间的关系。
通过三级成人和儿科胃肠病学中心招募了 798 名 CD 患者的队列，中位随访时间为 7 年。对疾病的详细表型描述进行了记录，包括临床表现、对治疗的反应和并发症。对先前文献中报道的 53 个 CD 相关变异进行了基因分型，并寻找与临床亚表型的相关性。使用包含 722 名 CD 患者的复制队列进一步探索了潜在的关联。
NOD2 罕见变异与较早的诊断年龄（p=0.0001）和回肠受累相关（rs2066844 和 rs2066847 的 OR 值分别为 2.25[1.49-3.41]和 2.77[1.71-4.50]）。结肠病变与 IL23R rs11209026 的风险等位基因呈正相关（OR=2.25[1.13-4.51]）和 6q21 rs7746082 的风险等位基因呈正相关（OR=1.60[1.10-2.34]），与 IRGM rs13361189 的风险等位基因呈负相关（OR=0.29[0.11-0.74]）和 DEFB1 rs11362 的风险等位基因呈负相关（OR=0.50[0.30-0.80]）。ATG16L1 和 IRGM 变体与非炎症性表型相关（OR=1.75[1.22-2.53]和 OR=1.50[1.04-2.16]）。然而，这些关联在多重测试校正后失去了意义。IRGM 风险等位基因对结肠病变的保护作用是第二个队列中唯一复制的关联（p=0.03）。
不建议在常规实践中对研究的多态性进行基因分型。
