Combined carriership of TLR9-1237C and CD14-260T alleles enhances the risk of developing chronic relapsing pouchitis

Combined carriership of TLR9-1237C and CD14-260T alleles enhances the risk of developing chronic relapsing pouchitis
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DOI:
10.3748/wjg.v11.i46.7323
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发表时间:
2005-12-14
影响因子:
4.3
通讯作者:
Pena, A. S.
Pena, A. S.
中科院分区:
医学2区
文献类型:
--
作者:
Lammers, K. M.;Ouburg, S.;Pena, A. S.

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目的:探讨细菌识别相关基因的单核苷酸多态性(SNPs)与小囊炎易感性及小囊炎严重程度的关系。方法:对157例回肠-袋肛瘘(IPAA)患者(未发生小囊炎79例、罕见小囊炎43例、慢性复发小囊炎35例)和224例意大利白种健康对照进行CD14 -260C>T、CARD15/NOD2 3020insC、toll样受体(TLR)4 + 896A>G、TLR9 -1237T>C、TLR9 + 2848G>A和IRAKM + 22148G>A snp分析。结果:对照组与IPAA患者SNP频率无显著差异。而TLR9 -1237C等位基因携带频率在罕见性和慢性复发性荷包炎组间差异有统计学意义[P = 0.028, odd’s ratio (OR) = 3.2, 95%CI = 1.2 ~ 8.6]。该等位基因在白种人中独特地代表了包含所研究的两个TLR9 snp的4位点TLR9单倍型。载体性状分析显示,TLR9 -1237C和CD14 -260T等位基因在慢性复发性和罕见性荷囊炎组中联合携带增强(P = 0.018, OR = 4.1, 95%CI = 1.4-12.3)。结论:没有证据表明snp易导致IPAA手术的需要。CD14 -260T和TLR9 -1237C等位基因在慢性复发性眼袋炎组中的联合携带显著增加,表明这些标记物可识别IPAA患者中有发生慢性或难治性眼袋炎风险的亚组。(C) 2005 WJG出版社和爱思唯尔公司。版权所有。
AIM: To investigate the single nucleotide polymorphisms (SNPs) in genes involved in bacterial recognition and the susceptibility to pouchitis or pouchitis severity.METHODS: Analyses of CD14 -260C>T, CARD15/NOD2 3020insC, Toll-like receptor (TLR)4 + 896A>G, TLR9 -1237T>C, TLR9 + 2848G>A, and IRAKM + 22148G>A SNPs were performed in 157 ileal-pouch anal anastomosis (IPAA) patients (79 patients who did not develop pouchitis, 43 infrequent pouchitis patients, 35 chronic relapsing pouchitis patients) and 224 Italian Caucasian healthy controls.RESULTS: No significant differences were found in SNP frequencies between controls and IPAA patients. However, a significant difference in carriership frequency of the TLR9 -1237C allele was found between the infrequent pouchitis and chronic relapsing pouchitis groups [ P = 0.028, odd's ratio (OR) = 3.2, 95%CI = 1.2-8.6]. This allele uniquely represented a 4-locus TLR9 haplotype comprising both studied TLR9 SNPs in Caucasians. Carrier trait analysis revealed an enhanced combined carriership of the alleles TLR9 -1237C and CD14 -260T in the chronic relapsing pouchitis and infrequent pouchitis group (P = 0.018, OR = 4.1, 95%CI = 1.4-12.3).CONCLUSION: There is no evidence that the SNPs predispose to the need for IPAA surgery. The significant increase of the combined carriership of the CD14 -260T and TLR9 -1237C alleles in the chronic relapsing pouchitis group suggests that these markers identify a subgroup of IPAA patients with a risk of developing chronic or refractory pouchitis. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.