Article (Scientific journals)
Analysis of Genes Associated With Monogenic Primary Immunodeficiency Identifies Rare Variants in XIAP in Patients With Crohn's Disease.
Amininejad, Leila; Charloteaux, Benoît; Theatre, Emilie et al.
2018In Gastroenterology, 154 (8), p. 2165-2177
Peer Reviewed verified by ORBi
 

Files


Full Text
amininejad2018.pdf
Author preprint (18.01 MB)
accepted manuscript
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
Candidate Gene Approach; Complex Trait; Inflammatory Bowel Disease; Mendelian Disorder
Abstract :
[en] BACKGROUND & AIMS: A few rare monogenic primary immunodeficiencies (PIDs) are characterized by chronic intestinal inflammation that resembles Crohn's disease (CD). We investigated whether 23 genes associated with 10 of these monogenic disorders contain common, low-frequency, or rare variants that increase risk for CD. METHODS: Common and low frequency variants in 1 Mb loci centered on the candidate genes were analyzed using meta-data corresponding to genotypes of approximately 17,000 patients with CD or without CD (controls) in Europe. The contribution of rare variants was assessed by high-throughput sequencing of 4750 individuals, including 660 early-onset and/or familial cases among the 2390 patients with CD. Variants were expressed from vectors in SW480 or HeLa cells and functions of their products were analyzed in immunofluorescence, luciferase, immunoprecipitation, and immunoblot assays. RESULTS: We reproduced the association of the interleukin 10 locus with CD (P = .007), although none of the significantly associated variants modified the coding sequence of interleukin 10. We found XIAP to be significantly enriched for rare coding mutations in patients with CD vs controls (P = .02). We identified 4 previously unreported missense variants associated with CD. Variants in XIAP cause the PID X-linked lymphoproliferative disease type 2, yet none of the carriers of these variants had all the clinical features of X-linked lymphoproliferative disease type 2. Identified XIAP variants S123N, R233Q, and P257A were associated with an impaired activation of NOD2 signaling after muramyl dipeptide stimulation. CONCLUSIONS: In a systematic analysis of variants in 23 PID-associated genes, we confirmed the association of variants in XIAP with CD. Further screenings for CD-associated variants and analyses of their functions could increase our understanding of the relationship between PID-associated genes and CD pathogenesis.
Disciplines :
Genetics & genetic processes
Author, co-author :
Amininejad, Leila 
Charloteaux, Benoît  ;  Université de Liège - ULiège > GIGA-Research
Theatre, Emilie 
Liefferinckx, Claire
Dmitrieva, Julia
Hayard, Pierre
Muls, Vincianne
Maisin, Jean-Marc
Schapira, Michael
Ghislain, Jean-Michel
Closset, Pierre
Talib, Mehdi
Abramowicz, Marc
Momozawa, Yukihide
Deffontaine, Valerie
Crins, Francois
Mni, Myriam
Karim, Latifa
Cambisano, Nadine
Ornemese, Sandra
Zucchi, Alessandro
Minsart, Charlotte
Deviere, Jacques
Hugot, Jean-Pierre
De Vos, Martine
Louis, Edouard  ;  Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Vermeire, Severine
Van Gossum, Andre
Coppieters, Wouter ;  Université de Liège - ULiège > Dpt. de gestion vétérinaire des Ressources Animales (DRA) > GIGA-R : Génomique animale
Twizere, Jean-Claude   ;  Université de Liège - ULiège > Agronomie, Bio-ingénierie et Chimie (AgroBioChem) > Microbial, food and biobased technologies
Georges, Michel   ;  Université de Liège - ULiège > Dpt. de gestion vétérinaire des Ressources Animales (DRA) > GIGA-R : Génomique animale
Franchimont, Denis 
More authors (22 more) Less
 These authors have contributed equally to this work.
Language :
English
Title :
Analysis of Genes Associated With Monogenic Primary Immunodeficiency Identifies Rare Variants in XIAP in Patients With Crohn's Disease.
Publication date :
2018
Journal title :
Gastroenterology
ISSN :
0016-5085
eISSN :
1528-0012
Publisher :
Elsevier
Volume :
154
Issue :
8
Pages :
2165-2177
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
Available on ORBi :
since 02 July 2018

Statistics


Number of views
86 (12 by ULiège)
Number of downloads
5 (5 by ULiège)

Scopus citations®
 
22
Scopus citations®
without self-citations
22
OpenCitations
 
24

Bibliography


Similar publications



Contact ORBi