Association of PSORS1C3, CARD14 and TLR4 genotypes and haplotypes with psoriasis susceptibility

Abstract

Psoriasis is a common chronic, immune-mediated inflammatory disease of the skin. PSORS1C3 is a non-protein coding gene, of which the RNA transcript is found in psoriatic patients. CARD14 is mainly expressed in epidermal keratinocytes. TLR4 is a transmembrane protein to recognize microbial antigens. Our study aimed to assess the relationship among PSORS1C3, CARD14 and TLR4 polymorphisms, inflammatory expression and psoriasis susceptibility. To the end, 71 patients with psoriasis and 46 healthy individuals with the well-characterized clinical profiles were enrolled. Gene polymorphisms were determined by Sanger DNA sequencing and secretion of cytokines by ELISA. As a result, genetic analysis of PSORS1C3 gene identified nine SNPs and three haplotype blocks. Sequencing of the CARD14 gene determined eight SNPs and one haplotype block. Sequencing of TLR4 gene identified nine SNPs, in which a SNP rs1018673641 was found to exert deleterious effect. The linkage disequilibrium analysis showed that seven variants in PSORS1C3 gene and three SNPs in CARD14 gene were in tightly linked. More importantly, a significant association between IL-6 level and rs1018673641 AT genotype in TLR4 gene was detected in psoriatic patients. In conclusion, the PSORS1C3, CARD14 and TLR4 polymorphisms and haplotypes may be correlated with risk of suffering psoriasis and the IL-6-mediated chronic inflammation in psoriasis could be partially regulated by the TLR4 functional variant.

Aberrant inflammasome activation as a driving force of human autoimmune skin disease

“…Furthermore, it is important to enlighten the complex interplay of regulatory mechanisms of inflammasomes and their dysregulation in disease. For instance, SNPs in CARD14 can entail – as gain-of-function variant in psoriasis – increased NF-κB signaling and thus expression of proinflammatory cytokines ( 201 ). The loss-of-function variant in CARD14 in atopic dermatitis leads to a decrease in NF-κB activation, epidermal secretion of antimicrobial peptides ( 202 ) and mRNA expression of FLG ( 203 ), encoding filaggrin, which is an epidermal protein essential for skin barrier function ( 204 ).…”

Revealing the intricacies: A comprehensive study of the CARD14 gene in Psoriatic patients of Indian descent

“…The proteins derived from these transcripts possess the ability to attract immune cells linked to disease's etiology 19,20 . Several chemokines were expressed when dermal endothelium cells were exposed to psoriatic cytokines in culture, including TNFα, IL-17, and IFN , like those upregulated following transfections of endothelial cells with mutations associated with psoriasislinked CARD14 [21][22][23] . Furthermore, it was found that co-localization of these numerous chemokines with dermal endothelial cells in their native environment and was enhanced in psoriatic lesions.…”