Genotype-phenotype associations of polymorphisms within the gene locus of NOD-like receptor pyrin domain containing 3 in Swiss inflammatory bowel disease patients

• Published in: BMC gastroenterology Vol. 21; no. 1; p. 310
• Main 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
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03-08-2021; BioMed Central; BMC
• Subjects: Alleles; Clinical characteristics; Cohort Studies; Colitis, Ulcerative - genetics; Crohn's disease; Cytokines; Gastroenterology; Genetic aspects; Genetic Association Studies; Genetic diversity; Genetic Predisposition to Disease; Genotype; Genotype & phenotype; Health aspects; Health risk assessment; Humans; IL-1β; Inflammasomes; Inflammatory bowel disease; Inflammatory Bowel Diseases; Interleukin 18; NLR Family, Pyrin Domain-Containing 3 Protein; NLR Proteins; NLRP3 inflammasome; Pathogenesis; Patients; Phenotypes; Polymorphism, Single Nucleotide; Pyrin Domain; Pyrin protein; Regression analysis; Risk factors; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Statistical analysis; Switzerland; Ulcerative colitis; Switzerland; Inflammatory bowel disease; Clinical characteristics; Single nucleotide polymorphisms; NLRP3 inflammasome
• ISSN: 1471-230X; 1471-230X
• DOI: 10.1186/s12876-021-01880-9

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).
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.
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.
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.