title: Genetic support for the role of the NLRP3 inflammasome in psoriasis susceptibility.
abstract: NACHT leucine-rich repeat- and PYD-containing (NLRP)3 protein controls the inflammasome by regulating caspase-1 activity and interleukin (IL)-1β processing. The contribution of IL-1β in the pathogenesis of psoriasis is well recognized. Polymorphisms in NLRP3 and caspase recruitment domain-containing protein (CARD)8, a negative regulator of caspase-1 activity, have been associated with susceptibility to common inflammatory diseases, such as Crohn's disease and rheumatoid arthritis. To investigate the role for genetic variants in the NLRP3 inflammasome in psoriasis susceptibility. In a patient sample comprising 1988 individuals from 491 families and 1002 healthy controls, genotypes for four selected single-nucleotide polymorphisms (SNPs) in NLRP3 (three SNPs) and CARD8 (one SNP) were determined by TaqMan(®) Allelic Discrimination. Using the transmission disequilibrium test (TDT), a significant increase in the transmission of the NLRP3 rs10733113G genotype to a subgroup of patients with more widespread psoriasis was demonstrated (P = 0.015). Using logistic regression analysis in 741 patients with psoriasis and 1002 controls, the CARD8 rs2043211 genotype was significantly different in cases and controls in overall terms [OR 1.3 (1.1-1.5), P = 0.004] and for both genders. Our data support the hypothesis that the inflammasome plays a role in psoriasis susceptibility.
authors.affiliation: Division of Cell Biology and Dermatology, Department of Clinical and Experimental Medicine, Ingrid Asp Psoriasis Research Center, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Carlström
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Ekman
authors.forename: Stina
authors.initials: S
authors.lastname: Petersson
authors.forename: Peter
authors.initials: P
authors.lastname: Söderkvist
authors.forename: Charlotta
authors.initials: C
authors.lastname: Enerbäck
mesh_terms: D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D058847:Inflammasomes / Q000235:genetics* / Q000276:immunology; D015810:Linkage Disequilibrium; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology*; D013548:Sweden
chemical_list: D053468:CARD Signaling Adaptor Proteins; C455623:CARD8 protein, human; D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D009363:Neoplasm Proteins; D020170:Caspase 1