Ingrid Asp Psoriasis Research Center, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85, Linköping, Sweden.
Br J Dermatol. 2014 Dec;171(6):1517-20. doi: 10.1111/bjd.13178. Epub 2014 Oct 22.
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.
The aim of the study was to investigate the role of genetic variation in the NLRP1 inflammasome in psoriasis susceptibility.
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.
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.
Our data support the involvement of NLRP1 and the NLRP1 inflammasome in psoriasis susceptibility and further support the role of innate immunity in psoriasis.
富含 NACHT、LRR 和 PYD 结构域的蛋白 1（NLRP）1 是炎症小体多蛋白复合物的一部分，该复合物参与白细胞介素（IL）-1β 和 IL-18 的产生，这两种细胞因子强烈参与银屑病的发病机制。NLRP1 中的遗传变异与慢性炎症性疾病的易感性有关。
本研究旨在探讨 NLRP1 炎症小体的遗传变异在银屑病易感性中的作用。
通过 TaqMan 等位基因鉴别法，在包括来自 478 个家庭的 1847 名个体和 802 名健康对照者的患者样本中，检测了 NLRP1 炎症小体的 4 个单核苷酸多态性（SNP）（rs6502867、rs8079034、rs878329 和 rs12150220）的单倍型标签 SNP。
通过传递不平衡检验，显示 NLRP1 rs8079034C 和 rs878329C 等位基因向银屑病患者的传递显著增加（P = 0.006 和 P = 0.033）。此外，rs878329C 等位基因的纯合性与发病年龄较早有关。我们还观察到银屑病患者外周血单个核细胞中 NLRP1mRNA 的表达增加。这伴随着循环 IL-18 水平的升高，并且似乎与 rs878329C 等位基因相关。
我们的数据支持 NLRP1 和 NLRP1 炎症小体在银屑病易感性中的作用，并进一步支持先天免疫在银屑病中的作用。
