证实自噬相关基因16样蛋白1（ATG16L1）作为克罗恩病易感基因的作用。

Confirmation of the role of ATG16L1 as a Crohn's disease susceptibility gene.

作者信息

Cummings J R Fraser, Cooney Rachel, Pathan Saad, Anderson Carl A, Barrett Jeffrey C, Beckly John, Geremia Alessandra, Hancock Laura, Guo Changcun, Ahmad Tariq, Cardon Lon R, Jewell Derek P

机构信息

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.

出版信息

Inflamm Bowel Dis. 2007 Aug;13(8):941-6. doi: 10.1002/ibd.20162.

DOI:10.1002/ibd.20162

PMID:17455206

Abstract

BACKGROUND

A German genome-wide nonsynonymous single nucleotide polymorphism (nsSNP) association study identified ATG16L1 as a Crohn's disease (CD) susceptibility gene. The association appeared to be confined to the nsSNP rs2,241,880 and was confirmed in 2 German independent case-control collections (combined P = 4.0 x 10(-8), odds ratio [OR] 1.45; 95% confidence interval [CI]: 1.21-1.74), a CD transmission disequilibrium test (TDT) collection, and an independent UK cohort. A weak statistical interaction with CARD15 was demonstrated. No association with ulcerative colitis (UC) was demonstrated. The aims of the study were to replicate the association with CD, examine subphenotype associations and statistical interactions with CARD15, IL23R, and the IBD5 risk haplotype, as well as explore the association with UC.

METHODS

The study included 645 CD and 676 UC rigorously phenotyped patients recruited from a single UK center. Unaffected controls comprised either spouses of patients (141) or individuals recruited from well-person clinics (1,049). The nsSNP rs2,241,880 was genotyped using MassArray (Sequenom).

RESULTS

A strong association with CD was demonstrated (P = 2.33 x 10(-7), OR 1.45 [1.25-1.67]), but no significant association was demonstrated with any subphenotype. We failed to replicate the reported interaction between rs2,241,880 and the CARD15 low-risk haplotypes dd and Dd. No significant statistical interaction with the 3 known CD susceptibility genes was seen. No association with UC susceptibility (P = 0.37, OR 1.06 [0.93-1.22]), or any UC subphenotype was identified.

CONCLUSIONS

We confirmed the findings that ATG16L1 is a CD susceptibility gene and found no evidence of interaction with CARD15, IL23R, or IBD5.

摘要

背景

一项德国全基因组非同义单核苷酸多态性（nsSNP）关联研究确定ATG16L1为克罗恩病（CD）易感基因。该关联似乎局限于nsSNP rs2241880，并在2个德国独立病例对照样本集（合并P = 4.0×10⁻⁸，优势比[OR] 1.45；95%置信区间[CI]：1.21 - 1.74）、一个CD传递不平衡检验（TDT）样本集以及一个独立的英国队列中得到证实。还证实了与CARD15存在微弱的统计学相互作用。未证实与溃疡性结肠炎（UC）有关联。本研究的目的是重复与CD的关联，研究亚表型关联以及与CARD15、IL23R和IBD5风险单倍型的统计学相互作用，同时探索与UC的关联。

方法

本研究纳入了从英国一个中心招募的645例CD患者和676例UC患者，这些患者均经过严格的表型分析。未受影响的对照包括患者的配偶（141例）或从健康诊所招募的个体（1049例）。使用MassArray（Sequenom）对nsSNP rs2241880进行基因分型。

结果

证实与CD存在强关联（P = 2.33×10⁻⁷，OR 1.45 [1.25 - 1.67]），但未证实与任何亚表型存在显著关联。我们未能重复报道的rs2241880与CARD15低风险单倍型dd和Dd之间的相互作用。未观察到与3个已知CD易感基因存在显著的统计学相互作用。未发现与UC易感性（P = 0.37，OR 1.06 [0.93 - 1.22]）或任何UC亚表型有关联。