Genetic variations of NLRP1: susceptibility in psoriasis
- PMID: 24909542
- DOI: 10.1111/bjd.13178
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.
Objectives: The aim of the study was to investigate the role of genetic variation in the NLRP1 inflammasome in psoriasis susceptibility.
Material and 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.
© 2014 British Association of Dermatologists.
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