患有炎症性肠病的贝都因阿拉伯人中NOD2/CARD15突变：频率与表型相关性

NOD2/CARD15 Mutations among Bedouin Arabs with Inflammatory Bowel Disease: Frequency and Phenotype Correlation.

作者信息

Abu Freha Naim, Badarna Wafi, Abu Tailakh Muhammad, Abu Kaf Heba, Fich Alex, Schwartz Doron, Segal Arik, Elkrinawi Jabir, Karban Amir

机构信息

Departments of Gastroenterology and Hepatology, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.

Department of Internal Medicine E, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.

出版信息

Isr Med Assoc J. 2018 Nov;20(11):695-699.

PMID:30430799

Abstract

BACKGROUND

Inflammatory bowel disease (IBD) prevalence is increasing among Bedouin Arabs in Israel. This population is known to have a high rate of consanguinity. NOD2/CARD15 mutations are well-studied in IBD.

OBJECTIVES

To investigate the frequency of NOD2/CARD15 mutations in IBD Bedouin patients and their relevance to disease phenotype.

METHODS

The IBD-Arab cohort in southern Israel included 68 patients, of which 25 Crohn's disease (CD) patients and 25 ulcerative colitis (UC) patients consented to participate (72%). Blood samples were obtained from all participants who were genotyped for NOD2/CARD15 variants Arg702Trp, Gly908Arg, and Leu1007fsinsC.

RESULTS

The NOD2/CARD15 mutation frequency was higher in Crohn's disease than in ulcerative colitis patients. Carrier frequency for the Gly908Arg mutation in CD and UC patients was 8/25 (32%) and 3/25 (12%), respectively (P = 0.08). Neither the Arg702Trp nor Leu1007fsinsC mutation was found in our cohort. No homozygous/compound heterozygote mutations were found. Genotype-phenotype analysis revealed that CD patients carrying the Gly908Arg mutation were younger at diagnosis, 22.8 ± 4.5 vs. 28.82 ± 9.1 years (P = 0.04). All carriers were males, compared with 41.2% in non-carriers (P = 0.005). NOD2/CARD15 mutation carriers with UC were older, 67.0 ± 24.5 years compared with 41.2 ± 12.3 years (P = 0.006). No other associations regarding disease localization or other clinical parameter were found.

CONCLUSIONS

The frequency of NOD2/CARD15 gene mutations is high in CD and UC among Bedouin Arab IBD patients and is associated with younger age at onset in CD and male gender.

摘要

背景

以色列贝都因阿拉伯人中炎症性肠病（IBD）的患病率正在上升。已知该人群近亲结婚率很高。NOD2/CARD15突变在IBD中已得到充分研究。

目的

调查IBD贝都因患者中NOD2/CARD15突变的频率及其与疾病表型的相关性。

方法

以色列南部的IBD-阿拉伯队列包括68名患者，其中25名克罗恩病（CD）患者和25名溃疡性结肠炎（UC）患者同意参与（72%）。从所有参与者中采集血样，对其进行NOD2/CARD15变异体Arg702Trp、Gly908Arg和Leu1007fsinsC的基因分型。

结果

NOD2/CARD15突变频率在克罗恩病患者中高于溃疡性结肠炎患者。CD和UC患者中Gly908Arg突变的携带频率分别为8/25（32%）和3/25（12%）（P = 0.08）。在我们的队列中未发现Arg702Trp和Leu1007fsinsC突变。未发现纯合子/复合杂合子突变。基因型-表型分析显示，携带Gly908Arg突变的CD患者诊断时年龄较小，分别为22.8±4.5岁和28.82±9.1岁（P = 0.04）。所有携带者均为男性，而非携带者中男性占41.2%（P = 0.005）。UC的NOD2/CARD15突变携带者年龄较大，为67.0±24.5岁，而对照组为41.2±12.3岁（P = 0.006）。未发现其他与疾病定位或其他临床参数相关的关联。