Gene-gene Interactions In IL23/Thl7Pathway Contribute To Psoriasis Susceptibility In Chinese Han Population

Background Psoriasis is a common chronic, hyperproliferative autoimmune skindisease. Numerous studies have proved that there was a strong genetic susceptibility anda multi-factorial etiology underlying psoriasis, in which gene-gene or gene-environmentinteractions may jointly affect the onset, manifestation and clinical course of psoriasis.IL23/Th17axis was newly identified pathway in the etiology of chronic inflammatorydiseases. The genes in this pathway were found to be associated with the risk ofpsoriasis. Based on these data, we hypothesize that gene-gene interactions within theIL23/Th17pathway might contribute to psoriasis susceptibility.Methods299single-nucleotide polymorphisms (SNPs) from11genes in IL23/Th17pathway were genotyped on1139patients with psoriasis and1694controls. Multifactordimensionality reduction (MDR) and logistic regression algorithms were applied to thegenotype data to explore the gene-gene interactions.Results We confirmed that there were genetic associations of IL12B（SNP rs7709212，OR=0.77、P=2.69E-6）and TNF（SNP rs3093662，OR=3.38、P=1.72E-30）genes withpsoriasis susceptibility in Chinese Han population. We found that there were athree-way interaction among IL21, CCR4and TNF(χ~2=5.02(1),p=0.025) and threepair-wise gene-gene interactions between IL12RB1and CCR4(χ~2=11.66(4),p=0.0201), IL22and CCR4(χ~2=11.97(4), p=0.0176), IL12RB1and IL6(χ~2=7.31(1),p=0.0069) inpsoriasis.Conclusions Our results provided strong evidences that the IL23/Th17pathway is a keyplayer in the development of psoriasis through gene-gene interactions.