Gene-gene Interaction Between LCE And CLEC16A Increases The Irsk To Psoirasis In The Chinese Han Population

Background Psoriasis is a common autoimmune cutaneous disorder characterized byinflammation and abnormal epidermal proliferation. Nowadays, it is believed that someinflammatory cells, such as dendritic cells, macrophages, neutrophils, keratinocytes, andseveral cytokines, appear to have important roles in the pathogenesis of psoriasis. Ourprevious genome-wide association study has provided convincing evidence that LCEgene cluster is a susceptibility factor of psoriasis, and simultaneously discovered theassociation between CLEC16A gene and psoriasis the (SNP rs193756, OR=0.8, P=0.0004). LCE multigene cluster encodes epidermal barrier proteins, and the expressionof LCE proteins was regulated by the combination of proinflammatory cytokines.CLEC16A gene has previously been found to be associated with multiple sclerosis, andCLEC16A protein is shown to be highly expressed on inflammatory cells. In addition,the interaction studies between LCE and HLA-C and among MHC locus, LCE andIL12B have also been conducted in large samples. The postulated common pathway ofLCE and CLEC16A between inflammatory response and epidermal barrier prompted usto examine the combined contribution of both genes to the susceptibility to psoriasis.Objective We evaluated the associations of genotypes of LCE rs4112788andCLEC16A rs193756with psoriasis, and determined the gene-gene interaction betweenLCE and CLEC16A on risk for psoriasis. Method we conducted genotypes of LCE rs4112788and CLEC16A rs193756in5101cases and6183controls, which were Chinese Han population and both from ourprevious GWAS, and established four different interactive models of LCE andCLEC16A. P values were estimated by Chi-square or Fisher exact tests. Interrelationswere analyzed by multiple logistic regression.Result LCE rs4112788-CC patients were observed at increased risk of psoriasis (OR=1.76, P=5.90×10-5), but the presence of CLEC16A rs193756genotypes were notobserved significant association with psoriasis. Under four different interactive modelsof LCE and CLEC16A, we observed the subjects carrying the LCE rs4112788-CC or-TC and the CLEC16A rs193756-GG had a suggestive significant interaction in the riskof developing psoriasis (OR=1.84, P=0.0605). This combined effect on psoriasis riskwas more significant when both genotypes were found in homozygosis, the LCErs4112788-CC and the CLEC16A rs193756-GG (OR=1.57, P=0.0053).Conclusion This study confirmed that combined actions of LCE and CLEC16A maylead to the worsening disease of psoriasis in the Chinese Han population, the LCErs4112788-CC and the CLEC16A rs193756-GG were at increased risk to psoriasis. Ourfindings provide a new clue that the interaction between the epidermal barrier and theinflammatory response system may be involved in the pathogenesis of psoriasis, whichsuggest that further studies are needed to confirm it.