Association Analysis Of CASR And TARBP1 Genes With Clinical Features Of Psoriasis Vulgaris In Chinese Han Population

Background Psoriasis is a common chronic inflammatory skin disease with multifactorial etiology. Even most scholars and specialist think that the psoriasis is the result of genetic and environmental interactions,and genetic factors are more essential to psoriasis risk.But the etiology and pathogenesis are not fully understood.Recently,we confirmed that the CASR( rs1042636) and TARBP1(rs744487) genes is associated with psoriasis vulgaris in our whole exome analysis,which was associated with psoriasis vulgaris at genome-wide significance in Chinese Han population.Objective: To investigate the genetic model for the CASR and TARBP1 mutation and to determine the correlation between this two genes and psoriasis vulgaris clinical phenotypes, including age of onset, the severity of disease, the skin lesion type of disease and family history, Thereby Determine if the gene for genetic contributions to different clinical phenotypes, in order to clear the pathogenesis of psoriasis.Method:The CASR and TARBP1 were sequenced in 9390 psoriasis vulgaris patients and 10800 controls from the Chinese population. Make comparisons of genotype and allele frequency distribution between each clinical subtypes and the control group, then observed the differences. The second step compared genotype and allele frequency distribution between each clinical subtypes between the cases, mainly the comparison of allele frequency, to observe distribution frequency of alleles in thecases,so as to identify the genetic contribution of this gene.SPSS 20.0 was used to investigate the relationship between the CASR and TARBP1 genotype and psoriasis vulgaris clinical phenotypes in Chinese Han population.Results: The A allele of CASR(P=1.88×10-10, OR=0.91,95%CI =0.89-0.94) and C allele of TARBP1(P=1.34×10-07,OR=1.09 95%CI=1.05-1.12)were observed to be significantly associated with psoriasis vulgaris. Analyses of the genetic model revealed that the Additive model best described the CASR mutation(P= 1.9×10-05),and the Additive model best described the TARBP1 mutation(P= 6.18×10-04). Stratified analyses showed that the CASR allele frequency distribution has no relationship with clinical phenotypes of psoriasis vulgaris in the Chinese Han population,the TARBP1 allele frequency distribution is significantly associated with Moderate disease severity(P=3.37×10-13, OR= 0.592, 95%CI=0.514-0.683), guttate skin lesion(P=0.027416, OR=1.082, 95%CI=1.009-1.160), and Family history(+)(P=0.011061, OR=1.115, 95%CI= 1.025-1.212).Conclusion: Our study indicates that the CASR and TARBP1 are associated with clinical phenotypes of psoriasis vulgaris in the Chinese Han population, which might help us gain a better understanding on the pathogenesis of psoriasis vulgaris.