Genotype–phenotype associations of polymorphisms within the gene locus of NOD-like receptor pyrin domain containing 3 in Swiss inflammatory bowel disease patients
Authors: Yoganathan Priyatharsan , Rossel Jean-Benoit , Jordi Sebastian Bruno Ulrich , Franc Yannick , Biedermann Luc , Misselwitz Benjamin , Hausmann Martin , Rogler Gerhard , Scharl Michael , Frey-Wagner Isabelle ,   Swiss IBD cohort study group, Abdelrahman Karim , Ademi Gentiana , Aepli Patrick , Thomas Amman , Anderegg Claudia , Antonino Anca-Teodora , Archanioti Eva , Arrigoni Eviano , Bakker de Jong Diana , Balsiger Bruno , Bastürk Polat , Bauerfeind Peter , Becocci Andrea , Belli Dominique , Bengoa José M. , Biedermann Luc , Binek Janek , Blattmann Mirjam , Boehm Stephan , Boldanova Tujana , Borovicka Jan , Braegger Christian P. , Brand Stephan , Brügger Lukas , Brunner Simon , Bühr Patrick , Burnand Bernard , Burk Sabine , Burri Emanuel , Buyse Sophie , Cao Dahlia-Thao , Carstens Ove , Criblez Dominique H. , Cunningham Sophie , D’Angelo Fabrizia , de Saussure Philippe , Degen Lukas , Delarive Joakim , Doerig Christopher , Dora Barbara , Drerup Susan , Egger Mara , El-Wafa Ali , Engelmann Matthias , Ezri Jessica , Felley Christian , Fliegner Markus , Fournier Nicolas , Fraga Montserrat , Franc Yannick , Frei Pascal , Frei Remus , Fried Michael , Froehlich Florian , Furlano Raoul Ivano , Garzoni Luca , Geyer Martin , Girard Laurent , Girardin Marc , Golay Delphine , Good Ignaz , Graf Bigler Ulrike , Gysi Beat , Haarer Johannes , Halama Marcel , Haldemann Janine , Heer Pius , Heimgartner Benjamin , Helbling Beat , Hengstler Peter , Herzog Denise , Hess Cyrill , Hessler Roxane , Heyland Klaas , Hinterleitner Thomas , Hirschi Claudia , Hruz Petr , Juillerat Pascal , Khalid-de Bakker Carolina , Kayser Stephan , Keller Céline , Knellwolf Christina , Knoblauch Christoph , Köhler Henrik , Koller Rebekka , Krieger Claudia , Künzler Patrizia , Kusche Rachel , Lehmann Frank Serge , Macpherson Andrew , Maillard Michel H. , Manz Michael , Marot Astrid , Meier Rémy , Meyenberger Christa , Meyer Pamela , Michetti Pierre , Misselwitz Benjamin , Mosler Patrick , Mottet Christian , Müller Christoph , Müllhaupt Beat , Musso Leilla , Neagu Michaela , Nichita Cristina , Niess Jan , Nydegger Andreas , Obialo Nicole , Ollo Diana , Oropesa Cassandra , Peter Ulrich , Peternac Daniel , Petit Laetitia Marie , Pittet Valérie , Pohl Daniel , Porzner Marc , Preissler Claudia , Raschle Nadia , Rentsch Ronald , Restellini Alexandre , Restellini Sophie , Richterich Jean-Pierre , Ris Frederic , Risti Branislav , Ritz Marc Alain , Rogler Gerhard , Röhrich Nina , Rossel Jean-Benoît , Rueger Vanessa , Rusticeanu Monica , Sagmeister Markus , Saner Gaby , Sauter Bernhard , Sawatzki Mikael , Scharl Michael , Schelling Martin , Schibli Susanne , Schlauri Hugo , Schluckebier Dominique , Schmid Daniela , Schmid Sybille , Schnegg Jean-François , Schoepfer Alain , Seematter Vivianne , Seibold Frank , Seirafi Mariam , Semadeni Gian-Marco , Senning Arne , Sokollik Christiane , Sommer Joachim , Spalinger Johannes , Spangenberger Holger , Stadler Philippe , Staub Peter , Staudenmann Dominic , Stenz Volker , Steuerwald Michael , Straumann Alex , Strebel Bruno , Stulz Andreas , Sulz Michael , Tatu Aurora , Tempia-Caliera Michela , Thorens Joël , Truninger Kaspar , Tutuian Radu , Urfer Patrick , Vavricka Stephan , Viani Francesco , Vögtlin Jürg , Von Känel Roland , Vouillamoz Dominique , Vulliamy Rachel , Wiesel Paul , Wiest Reiner , Wöhrle Stefanie , Zamora Samuel , Zander Silvan , Wylie Tina , Zeitz Jonas , Zimmermann Dorothee 
Published: November 2021

Abstract
Background
Genetic variations within the regulatory region of the gene encoding NOD-like receptor pyrin domain containing 3 (NLRP3) have been associated with Crohn’s Disease (CD). NLRP3 is part of the NLRP3-inflammasome that mediates the maturation of IL-1β and IL-18. Carrying the major allele of the single nucleotide polymorphisms (SNPs) rs10733113, rs4353135 and rs55646866 is associated with an increased risk for CD. We here studied the impact of these polymorphisms on clinical characteristics in patients of the Swiss IBD Cohort Study (SIBDCS).

Methods
We included 981 Crohn’s disease (CD) patients and 690 ulcerative colitis (UC) patients of the SIBDCS. We analyzed whether three CD-associated NLRP3 polymorphisms have an impact on the clinical disease course in these patients.

Results
In CD patients presence of the major allele (G) of rs10733113 was associated with less surgeries and lower maximal CDAI and a similar trend was observed for rs55646866 and rs4353135. Presence of the major allele of all three SNPs was negatively correlated to maximal CDAI. In UC patients homozygous genotype for the major allele (CC) for rs55646866 was associated with a higher age at diagnosis and a higher MTWAI index. Homozygous genotype for the major allele of all three polymorphisms was associated with a higher number of ambulatory visits and longer hospital stays.

Conclusions
In CD patients presence of the major allele of all three polymorphisms was associated with markers of a less severe disease course, while in UC the homozygous genotype for all major alleles suggested a more severe disease activity.