Variant Analysis Of IL36RN,CARD14 And AP1S3 In A Chinese Han Population With Generalized Pustular Psoriasis

Background: Generalized pustular psoriasis(GPP)is a rare life-threatening inflammatory skin disorder.GPP is one of the polygenic disease.Some scholars suggest that GPP alone is an independent type of pustular dermatosis and GPP with PV is a serious type of expression of psoriasis.Objective: We aimed to detect IL36 RN,CARD14 and AP1S3 mutations in a Chinese Han population;to identify the association between GPP and the above three genes,to analysis genetic heterogeneity between GPP alone and GPP with PV and to performed genotype-phenotype correlations of IL36 RN mutations.Methods: Coding exons of IL36 RN,CARD14 and AP1S3 were sequenced in 107 Chinese GPP patients.Subgroup analysis of IL36 RN and CARD14 mutations and genotype-phenotype correlations of IL36 RN mutations was performed within the GPP cohort.Results: We detected three new,five known rare mutations and one known low-frequency mutation in the exon of IL36RN: p.Arg10 Gln,p.Leu78 Pro,p.Tyr89 X,p.Asn47 Ser,p.Arg48 Trp,p.Pro76 Leu,p.Arg102 Trp,p.Glu112 Lys and c.115+6T>C.We detected three new and one known low-frequency mutations in the exon of CARD14: c.1356+4C>T,p.Val758 Met,p.Ala825 Thr,p.Asp176His(rs144475004).No rare variants in AP1S3 were identified in all 107 GPP patients.Significant differences of frequencies of IL36 RN mutations were observed between GPP and PV/ controls groups,GPP alone and GPP with PV groups.Significant difference of frequencies of CARD14 mutations were observed between GPP alone and GPP with PV groups,but none of it between GPP and PV/ controls groups.Three phenotypes--early age of disease onset,more markedly risk of recurrent trouble and systemic inflammation were found to be significantly associated with IL36 RN mutations carriers.Conclusions: Our results suggested mutations in IL36 RN were disease-causing factors in Chinese patients with GPP alone,and mutations in CARD14 were disease-causing factors with GPP with PV.But AP1S3 mutations were found to have nothing to do with Chinese Han patients with GPP.IL36 RN mutations carriers manifested a strikingly more severe clinical phenotype.