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Interleukin‐10 family cytokines pathway: genetic variants and psoriasis
Author(s) -
Galimova E.,
Rätsep R.,
Traks T.,
Kingo K.,
EscottPrice V.,
Kõks S.
Publication year - 2017
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.15363
Subject(s) - single nucleotide polymorphism , multifactor dimensionality reduction , haplotype , gene cluster , allele , genetics , psoriasis , genotyping , odds ratio , gene , genetic association , genotype , medicine , immunology , biology
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 IL 10 gene cluster were associated with psoriasis. Objectives To analyse the relationship between genetic polymorphisms in the IL 10 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 ( SNP s) of the IL 10 gene cluster. Genotyping for the SNP s was conducted on the Applied Biosystems 3730 DNA Analyzer using SNP lex ® technology. Generalized multifactor dimensionality reduction ( GMDR ) analysis was applied to discover a likely gene–gene interaction model among the SNP s. Results The results showed that the allele distributions of IL 10 gene cluster SNP s are significantly different between the case and control groups. Carriers of the IL 10 T allele (rs1554286) and the IL 20 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 IL 10 (rs1554286) and IL 20 (rs1518108) variants. The strongest protective effect was found with the block 1 haplotype ACATA in the IL 10 gene ( Pc = 0·004). Conclusions This study presents a novel finding that the combination of the two SNP s, IL 10 (rs1554286) and IL 20 (rs1518108), is associated with a reduced risk of psoriasis. Our results indicate that genetic variants of the immunomodulatory IL 10 and IL 20 genes may offer a protective effect in Europeans from Russia. Independent studies are required to verify the results and find a possible functional explanation.