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Br J Dermatol. 2014 Dec;171(6):1517-20. doi: 10.1111/bjd.13178. Epub 2014 Oct 22.

Genetic variations of NLRP1: susceptibility in psoriasis.

Author information

1
Ingrid Asp Psoriasis Research Center, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85, Linköping, Sweden.

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.

PMID:
24909542
DOI:
10.1111/bjd.13178
[Indexed for MEDLINE]

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