Interleukin‐10 family cytokines pathway: genetic variants and psoriasis. (21st April 2017)

• Record Type: Journal Article
• Authors: Galimova, E.; Rätsep, R.; Traks, T.; Kingo, K.; Escott‐Price, V.; Kõks, S.
• Is Part Of: British journal of dermatology. Volume 176:Number 6(2017)
• Page Start: 1577
• Page End: 1587
• Publication Date: 2017-04-21
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.15363
• Languages: English
• ISSNs: 0007-0963

Abstract

Abstract : What's already known about this topic? Psoriasis is a chronic immune‐mediated inflammatory skin disorder caused by a complex interplay between genetic and environmental factors. One unifying hypothesis of psoriasis pathophysiology is the cytokine network model. In this model either an endogenous stimulus such as HIV‐1, neuropeptides and/or medications, or an exogenous stimulus such as trauma, are represented as triggering a plexus of cellular events by inciting a cascade of cytokines. What does this study add? Our preliminary data suggest that the two polymorphisms rs1554286 and rs1400986, located in the IL10 gene cluster related to inflammatory and immunity processes, showed an association with protection against psoriasis. Our findings suggest evidence for a two‐locus interaction between the IL10 (rs1554286) and IL20 (rs1518108) variants in the risk of psoriasis, and highlight further the importance of multilocus effects in the genetic component of psoriasis. Haplotype analysis revealed an association of IL10 haplotype ACATA with a reduced risk for psoriasis. What is the translational message? Genetic investigation can provide key information about both the function of such genes in the immune system and the molecular mechanisms of psoriasis, which is expected to lead to the development of targeted precision therapies. Respond to this article Linked Comment:Traupe. Br J Dermatol 2017; 176:1438–1439 Summary: Background: Interleukin (IL)‐10 family cytokines IL‐10, IL‐19, IL‐20 and IL‐24 have been implicated in autoimmune diseases and we have previously reported that genetic variants in the IL10 gene cluster were associated with psoriasis. Objectives: To analyse the relationship between genetic polymorphisms in the IL10 gene cluster and psoriasis. This study also explores whether there are gene–gene interactions among these genetic polymorphisms. Methods: A total of 377 patients with psoriasis and 403 matched healthy controls were enrolled to carry out a case–control study for 48 single‐nucleotide polymorphisms (SNPs) of the IL10 gene cluster. Genotyping for the SNPs was conducted on the Applied Biosystems 3730 DNA Analyzer using SNPlex ® technology. Generalized multifactor dimensionality reduction (GMDR) analysis was applied to discover a likely gene–gene interaction model among the SNPs. Results: The results showed that the allele distributions of IL10 gene cluster SNPs are significantly different between the case and control groups. Carriers of the IL10 T allele (rs1554286) and the IL20 T allele (rs1400986) conferred protection from psoriasis [odds ratio (OR) = 0·63, corrected P ‐value ( Pc ) = 0·007; OR = 0·62, Pc = 0·038, respectively]. GMDR analysis displayed a significant gene–gene interaction between IL10 (rs1554286) and IL20 (rs1518108) variants. The strongest protective effect was found with the block 1 haplotype ACATA in the IL10 gene ( Pc = 0·004). Conclusions: This study presents a novel finding that the combination of the two SNPs, IL10 (rs1554286) and IL20 (rs1518108), is associated with a reduced risk of psoriasis. Our results indicate that genetic variants of the immunomodulatory IL10 and IL20 genes may offer a protective effect in Europeans from Russia. Independent studies are required to verify the results and find a possible functional explanation.