Genotype/phenotype analyses for 53 Crohn's disease associated genetic polymorphisms.
Genotype/phenotype analyses for 53 Crohn's disease associated genetic polymorphisms.
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DOI：
10.1371/journal.pone.0052223
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hugot JP
中科院分区：
文献类型：
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作者：
Jung C;Colombel JF;Lemann M;Beaugerie L;Allez M;Cosnes J;Vernier-Massouille G;Gornet JM;Gendre JP;Cezard JP;Ruemmele FM;Turck D;Merlin F;Zouali H;Libersa C;Dieudé P;Soufir N;Thomas G;Hugot JP
最近的研究报道了超过70个基因或位点在克罗恩病（CD）易感性中的作用。然而，这些协会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的53个CD相关多态性的基因型和表型之间的关系。由三级成人和儿科胃肠病中心招募了798例CD患者，中位随访时间为7年。记录了疾病的详细表型描述，包括临床表现、治疗反应和并发症。对参与者进行了先前文献中报道的53种CD相关变异的基因分型，并搜索了与临床亚表型的相关性。一个由722名CD患者组成的重复队列被用来进一步探讨假定的相关性。NOD 2罕见变异与早期诊断年龄（p = 0.0001）和回肠受累相关（rs 2066844和rs 2066847的OR分别为2.25[1.49-3.41]和2.77 [1.71-4.50]）。 结肠病变与IL 23 R rs 11209026（OR = 2.25 [1.13-4.51]）和6 q21 rs7746082（OR = 1.60 [1.10-2.34]）的风险等位基因正相关，与IRGM rs 13361189（OR = 0.29 [0.11-0.74]）和DEFB 1 rs 11362（OR = 0.50 [0.30-0.80]）的风险等位基因负相关。 ATG 16 L1和IRGM变体与非炎症行为相关（OR分别为1.75 [1.22-2.53]和OR =1.50 [1.04-2.16]）。 然而，这些关联在多次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队列中复制的唯一关联（p = 0.03）。 不建议在常规实践中对所研究的多态性进行基因分型。
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.
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影响因子：
30.8
作者：
Hampe, Jochen;Franke, Andre;Schreiber, Stefan
通讯作者：
Schreiber, Stefan
影响因子：
4.9
作者：
Lappalainen, Maarit;Halme, Leena;Paavola-Sakki, Paulina
通讯作者：
Paavola-Sakki, Paulina
影响因子：
30.8
作者：
Kugathasan, Subra;Baldassano, Robert N.;Bradfield, Jonathan P.;Sleiman, Patrick M. A.;Imielinski, Marcin;Guthery, Stephen L.;Cucchiara, Salvatore;Kim, Cecilia E.;Frackelton, Edward C.;Annaiah, Kiran;Glessner, Joseph T.;Santa, Erin;Willson, Tara;Eckert, Andrew W.;Bonkowski, Erin;Shaner, Julie L.;Smith, Ryan M.;Otieno, F. George;Peterson, Nicholas;Abrams, Debra J.;Chiavacci, Rosetta M.;Grundmeier, Robert;Mamula, Petar;Tomer, Gitit;Piccoli, David A.;Monos, Dimitri S.;Annese, Vito;Denson, Lee A.;Grant, Struan F. A.;Hakonarson, Hakon
通讯作者：
Hakonarson, Hakon
影响因子：
4.5
作者：
Libioulle C;Louis E;Hansoul S;Sandor C;Farnir F;Franchimont D;Vermeire S;Dewit O;de Vos M;Dixon A;Demarche B;Gut I;Heath S;Foglio M;Liang L;Laukens D;Mni M;Zelenika D;Van Gossum A;Rutgeerts P;Belaiche J;Lathrop M;Georges M
通讯作者：
Georges M
影响因子：
30.8
作者：
通讯作者：
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