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白细胞介素10(IL-10)基因变异与儿童期克罗恩病易感性

Interleukin 10 (IL-10) gene variants and susceptibility for paediatric onset Crohn's disease.

作者信息

Amre D K, Mack D R, Morgan K, Israel D, Lambrette P, Costea I, Krupoves A, Fegury H, Dong J, Grimard G, Deslandres C, Levy E, Seidman E G

机构信息

Department of Pediatrics, University of Montreal, Montreal, QC, Canada.

出版信息

Aliment Pharmacol Ther. 2009 May 1;29(9):1025-31. doi: 10.1111/j.1365-2036.2009.03953.x. Epub 2009 Feb 7.

Abstract

BACKGROUND

A recent genome-wide association study in adult patients with ulcerative colitis (UC) has implicated the interleukin 10 (IL-10) gene as an important candidate gene. Moreover, a UC-associated single nucleotide polymorphism (SNP) rs3024405 was also significantly associated with adult Crohn's disease (CD).

AIMS

To examine whether IL-10-CD associations extended to paediatric-onset CD.

METHODS

We implemented the case-control design at three paediatric gastroenterology clinics in Canada. CD patients (<or=20 years) were recruited along with healthy controls. DNA samples were genotyped for tag-single nucleotide polymorphisms (tag-SNPs) in the IL-10 gene. Allelic, genotype and haplotype associations with CD were studied.

RESULTS

A total of 270 patients and 336 controls were studied. The mean age (+/-s.d.) at diagnosis was 12.1 (+/-3.5). There were a slightly higher proportion of male patients (56.3%). Of the five IL-10 tag-SNPs, rs2222202 (C/T) (P = 0.03) and rs1800871 (C/T) (P = 0.05) showed significant allelic associations with CD. Specific IL-10 SNPs were associated with CD disease location and/or disease behaviour.

CONCLUSIONS

Our gene-wide analysis replicates recent findings of associations between IL-10 and adult CD, and suggests that these associations extend to paediatric-onset CD as well.

摘要

背景

近期一项针对成年溃疡性结肠炎(UC)患者的全基因组关联研究表明,白细胞介素10(IL-10)基因是一个重要的候选基因。此外,一种与UC相关的单核苷酸多态性(SNP)rs3024405也与成年克罗恩病(CD)显著相关。

目的

研究IL-10与CD的关联是否也存在于儿童期发病的CD中。

方法

我们在加拿大的三家儿科胃肠病诊所采用病例对照设计。招募了年龄小于或等于20岁的CD患者以及健康对照。对IL-10基因中的标签单核苷酸多态性(tag-SNP)进行DNA样本基因分型。研究了等位基因、基因型和单倍型与CD的关联。

结果

共研究了270例患者和336例对照。诊断时的平均年龄(±标准差)为12.1(±3.5)岁。男性患者比例略高(56.3%)。在五个IL-10标签SNP中,rs2222202(C/T)(P = 0.03)和rs1800871(C/T)(P = 0.05)与CD存在显著的等位基因关联。特定的IL-10 SNP与CD的病变部位和/或疾病行为相关。

结论

我们的全基因分析重复了近期关于IL-10与成年CD关联的研究结果,并表明这些关联也存在于儿童期发病的CD中。

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