Interleukin-10 family cytokines pathway: genetic variants and psoriasis

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 IL10 gene cluster were associated with psoriasis.

Objective

To analyze the relationship of genetic polymorphisms in the IL10 gene cluster with 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 SNPs of 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 likely gene–gene interaction model among the SNPs.

Results

The results showed that the alleles distributions of IL10 gene cluster SNPs are significantly different between case and control groups. Carriers of IL10 T allele (rs1554286) and of IL20 T allele (rs1400986) conferred protection to psoriasis (OR = 0.63, 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

The novel finding of the present study is gene-gene interaction of the IL-10 pathway on the reduced risk of psoriais. Our results indicate that genetic variants of the immunomodulatory IL10 and IL20 genes may protective effect in the Europeans from Russia. Independent studies are needed to verify the results and find the possible functional explanation.

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