Mutation Analysis Of The IL36RN Gene In Chinese Patients With Generalized Pustular Psoriasis

Background: Generalized pustular psoriasis (GPP) is a rare type of psoriasis characterizedby sudden and repeated episodes of generalized rash and disseminated pustules, oftenaccompanied by high-grade fever.Severe episodic attacks can be triggered by pregnancy,infections, and exposure to drugs. Recently, it have been reported that IL36RN mutations inrecessive (homozygous/compound heterozygous) states were causative for GPP, and manyheterozygous IL36RN variants were reported as predisposing factors for GPP. Besides,although GPP is traditionally held to be a variant of psoriasis,it has been demonstrated to bedifferent on etiology. It is clinically recognized that GPP could be divided into two sets ofgroups: GPP without psoriasis vulgaris (PV)(GPP alone) and GPP with preceding, later oraccompanied by PV(GPP with PV). Recently, a Japanese team first found the geneticheterogeneity between two subtypes of GPP from Japan, and they put forward that the GPPalone was caused by IL36RN mutations and GPP with PV may be a severe syndrome of PVwith pustular eruptions. Lately, Li Ming’s team reported that the frequency of IL36RN genemutations was significant difference between Chinese pediatric-onset GPP (PGPP) andadult-onset GPP (AGPP). Objective: In order to do further investigate about the genetic heterogeneity of GPP and PV,GPP alone and GPP with PV, PGPP and AGPP, here we performed a sanger sequencing toidentify IL36RN mutations in Chinese Han GPP and PV patients.Methods: Genomic DNA was extracted from the peripheral blood of62Chinese Han patientswith sporadic GPP, including17GPP alone cases VS45GPP with PV cases;16PGPP VS46AGPP cases. We included96healthy controls and174patients with PV. Polymerase chainreaction(PCR) and direct sequencing of the IL36RN gene were performed to identify andconfirm the mutations in the patients.Results: We found two novel variants and four known IL36RN mutations in29GPP patients,eighteen individuals carried recessive (homozygous/compound heterozygous) alleles and11cases harbored a single heterozygous change.Twelve PV patients and six controls harbored asingle heterozygous for three out of the six mutations.Significant differences were observed between GPP and PV groups, GPP alone and GPP withPV groups when compared frequencies of IL36RN variants, but we did not found associationbetween PGPP and AGPP groups.Conclusion: We found two unreported IL36RN variants, further confirmed mutations inIL36RN were predisposing factors in Chinese GPP patients, and provided more evidence thatGPP and PV are caused by different pathogenesis，in addition，we considered that GPP alonecould be regarded as an especial entities of GPP which is different from GPP with PV on theetiology.