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Genetic variations of NLRP 1 : susceptibility in psoriasis
Author(s) -
Ekman A.K.,
Verma D.,
Fredrikson M.,
Bivik C.,
Enerbäck C.
Publication year - 2014
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.13178
Subject(s) - inflammasome , psoriasis , allele , haplotype , single nucleotide polymorphism , genetic predisposition , immunology , genetics , medicine , biology , inflammation , genotype , gene
Summary 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 NLRP 1 are associated with a predisposition for chronic inflammatory conditions. Objectives The aim of the study was to investigate the role of genetic variation in the NLRP 1 inflammasome in psoriasis susceptibility. Material and methods Four haplotype‐tagging single‐nucleotide polymorphisms ( SNP s) (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 NLRP 1 and the NLRP 1 inflammasome in psoriasis susceptibility and further support the role of innate immunity in psoriasis.