Interleukin-10 family cytokines pathway: genetic variants and psoriasis

Galimova, E, Ratsep, R, Traks, T, Kingo, K, Escott-Price, V and Koks, S ORCID: 0000-0001-6087-6643 (2017) Interleukin-10 family cytokines pathway: genetic variants and psoriasis. BRITISH JOURNAL OF DERMATOLOGY, 176 (6). pp. 1577-1587.

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Abstract

<h4>Background</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.

Item Type:	Article
Uncontrolled Keywords:	Humans, Psoriasis, Genetic Predisposition to Disease, Interleukins, Interleukin-10, Case-Control Studies, Epistasis, Genetic, Heterozygote, Polymorphism, Single Nucleotide, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Russia, Female, Male, Genetic Variation, Young Adult, White People
Depositing User:	Symplectic Admin
Date Deposited:	14 Jul 2017 08:18
Last Modified:	13 Feb 2023 23:25
DOI:	10.1111/bjd.15363
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3008439