Variant Analysis Of IL36RN、CARD14、AP1S3 In Chinese Han Population With Palmoplantar Pustulosis

BackgroundPalmoplantar pustulosis(PPP)is a localized pustular psoriasis characterized by crops of sterile pustules on the palms and soles.The disease usually has a chronic and relapsing course and is resistant to treatment.Genetic predisposition of host has been implicated to play an important role in the pathogenesis of PPP in studies of association with the HLA genes by Japanese and other scholars.As both PPP and generalized pustular psoriasis(GPP)are variants of pustular psoriasis,the genes that contribute to GPP were validated in PPP.In recent years,with the development of gene sequencing techniques and genetic diagnostics,it has been shown that mutations in the IL36RN,CARD14 and AP1S3 genes are associated with GPP.It has been found that PPP is associated with mutations in AP1S3,but not with mutations in IL36RN and CARD14 in European patients.Similar results were reported in 88 cases of Japanese PPP which targeted the mutations of IL36RN.However,mutations in IL36RN were found in 2/14(14.3%)Chinese PPP patients.In addition,the relationship between mutations in CARD14 and APIS3 and PPP has not been clarified in Chinese population.ObjectiveTo explore the association between mutations in the IL36RN,CARD14 and AP1S3 genes and PPP in Chinese Han population.MethodsThis study included 96 patients with PPP and 336 healthy controls.Peripheral whole blood DNA was extracted according to the TGuide Large Volume Blood Genomic DNA Kit(Tiangen Biochemical Technology Ltd.,Beijing).All exons and flanking sequences of the IL36RN,CARD14 and AP1S3 genes were amplified by polymerase chain reaction(PCR)and sequenced.The gene mutation rate was compared between PPP group and healthy control group.Statistical analysis was performed using Pearson’s chi-square test or Fisher’s exact test.Results1.IL36RN gene sequencing was performed in 96 PPP cases and 144 healthy controls.Two known heterozygous mutations,c.115+6T>C(p.Arg10ArgX1)and c.140A>G(p.Asn47Ser),were detected:6(6.3%)of 96 PPP cases were identified to carry mutations with 3 carried c.115+6T>C and others carried c.140A>G,6(4.2%)of 144 healthy controls were identified to carry mutations with 2 carried c.115+6T>C and 4 carried c.140A>G.There was no significant difference in the mutation rate of IL36RN between PPP group and healthy control group(P = 0.67).2.CADR14 gene sequencing was performed in 96 PPP cases and 336 healthy controls.Three novel,rare heterozygous missense mutations:c.149G>A(p.Cys50Tyr),c.1436C>G(p.Pro479Arg),and c.1942G>A(p.Gly648Ser)were found.Each variant was predicted to have a damaging effect on the protein function according to the prediction of SIFT(Sorting Intolerant from Tolerant).The total frequency of these three variants was 3.1%in PPP patients,but none was found in controls.It was suggested that there was a significant association between CARD14 and PPP(P =0.01 1).3.AP1S3 gene sequencing was performed in 96 PPP cases and 336 healthy controls.No rare mutations and SNP sites were identified.ConclusionThe mutations in CARD14 gene may be related to PPP in Chinese Han population.The mutations in IL36RN and AP1S3 may not be associated with PPP in Chinese Han population.Our study provides new genetic insight into the mechanism of PPP development.