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

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.

Impact of NLRP3 gene polymorphisms (rs10754558 and rs10733113) on HPV infection and cervical cancer in southern Chinese population

“…In contrast, there have been fewer studies examining the association between the NLRP3 rs10733113 polymorphism and disease. However, rs10733113 has been linked to elevated Crohn’s disease risk, and the rs10733113 G allele is reportedly associated with a reduction in the need for surgery and in maximal disease activity in patients with Crohn’s disease [ 17 ]. The rs10733113 G allele is also reportedly associated with an early-onset skin disease in psoriatic arthritis patients [ 18 ].…”

“…This SNP has been linked to many different diseases including diabetes, COVID-19, and bladder cancer [ 14 – 16 ]. The rs10733113 polymorphism in the NLRP3 gene has also been studied in the context of inflammatory bowel disease [ 17 ] and psoriatic arthritis [ 18 ], although its relationship with cancer remains to be studied at length. The association between the NLRP3 rs10754558 and rs10733113 polymorphisms and CC risk remains to be characterized.…”

NOD-like receptors mediate homeostatic intestinal epithelial barrier function: promising therapeutic targets for inflammatory bowel disease

“… 44 The NLRP3 inflammasome plays a significant role in the pathogenesis of colitis, although NLRP3 was found to have both protective and disadvantageous functions in studies on mucosal immunity. Different results are associated, for example, with the mouse/human genetic backgrounds, 62 according to the composition of the gut microbiota, 63 with different colitis models, 64 or according to the method of inducing colitis (the concentration of DSS, the continuance of DSS delivery, and the number of cycles).…”

NLRP3 inflammasome in digestive diseases: From mechanism to therapy

“…Studies indicate that some genotypes of the NLRP3 inflammasome may be associated with the affectability of patients with IBD and could represent biomarkers for the evaluation of IBD severity. A Swiss cohort study found that three NLRP3-related single nucleotide polymorphisms (RS10733113, RS55646866, rs4353135) were negatively related to CD ( 145 ). Moreover, some negative results were found ( 146 ).…”