title: Genetic variations of NLRP1: susceptibility in psoriasis.
abstract: BACKGROUND
  NACHT, LRR and PYD domain-containing protein (NLRP)1 is part of the inflammasome multiprotein complex involved in the production of interleukin (IL)-1β and IL-18, two cytokines strongly implicated in psoriasis pathogenesis. Genetic variations in NLRP1 are associated with a predisposition for chronic inflammatory conditions.
  
  
  OBJECTIVE
  The aim of the study was to investigate the role of genetic variation in the NLRP1 inflammasome in psoriasis susceptibility.
  
  
  METHODS
  Four haplotype-tagging single-nucleotide polymorphisms (SNPs) (rs6502867, rs8079034, rs878329 and rs12150220) were investigated by TaqMan allelic discrimination in a patient sample comprising 1847 individuals from 478 families and 802 healthy controls.
  
  
  RESULTS
  Using the transmission disequilibrium test, a significant increase in the transmission of the NLRP1 rs8079034C and rs878329C alleles to patients with psoriasis was demonstrated (P = 0·006 and P = 0·033, respectively). Furthermore, homozygosity for the rs878329C allele correlated with a younger age of onset. We also observed an increase in the expression of NLRP1 mRNA in the peripheral blood cells of patients with psoriasis. This was accompanied by a higher level of circulating IL-18 and appeared to be associated with the rs878329C allele.
  
  
  CONCLUSIONS
  Our data support the involvement of NLRP1 and the NLRP1 inflammasome in psoriasis susceptibility and further support the role of innate immunity in psoriasis.
authors.affiliation: Ingrid Asp Psoriasis Research Center, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85, Linköping, Sweden.
authors.forename: A-K
authors.initials: AK
authors.lastname: Ekman
authors.forename: D
authors.initials: D
authors.lastname: Verma
authors.forename: M
authors.initials: M
authors.lastname: Fredrikson
authors.forename: C
authors.initials: C
authors.lastname: Bivik
authors.forename: C
authors.initials: C
authors.lastname: Enerbäck
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D058847:Inflammasomes / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics / Q000276:immunology; D000070576:NLR Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000276:immunology; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology; D012044:Regression Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D058847:Inflammasomes; D000070576:NLR Proteins; C427903:NLRP1 protein, human