Association between mutation of interleukin 36 receptor antagonist and generalized pustular psoriasis: A PRISMA-compliant systematic review and meta-analysis

BACKGROUND: Generalized pustular psoriasis (GPP) is a systemic inflammatory disease with poor outcomes, and several studies have suggested that the mutation of the interleukin 36 receptor antagonist gene (IL36RN) is related to GPP, where the polymorphism c.115+6T>C is reported to be the most common mutation of IL36RN. This study was performed to clarify and comprehensively evaluate the relationship between IL36RN gene polymorphism and the susceptibility of GPP subtypes. METHODS: To conduct a thorough literature review, studies were obtained using databases such as Pubmed, EMBASE, Cochrane, China National Knowledge Infrastructure, and the Wanfang database. Only studies published up to December 2019 were included. The quality of the research studies was estimated using the Newcastle–Ottawa scale. The total odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were pooled and analysed using STATA 14. The publication bias was evaluated through the Egger test, performed using the aforementioned software. Five common gene models were built and analysed to assess the association between the polymorphism c.115+6T>C and subtypes of GPP. RESULTS: A total of 10 studies were selected, including 683 cases of GPP patients. Meta-analyses showed that there was a significant statistical correlation of IL36RN mutation between GPP with or without psoriasis vulgaris (OR = 3.82, 95%CI 2.63–5.56) and between adult GPP and paediatric GPP (OR = 0.42, 95%CI 0.23–0.77). No obvious discrepancy between European patients (OR = 4.03, 95%CI 2.23–7.26) and Asian patients was found. The gene models showed clear associations between the polymorphism c.115+6T>C and GPP through the dominant model (CC+ TC vs TT, OR 2.74, 95%CI 2.06–3.64), recessive model (CC vs CT + TT, OR 4.33, 95%CI 2.84–6.60), homozygote model (CC vs TT, OR 4.37, 95%CI 2.88–6.62), heterozygote model (CT vs TT, OR 2.26, 95%CI 1.32–3.85) and allelic model (C vs T, OR 3.35, 95%CI 2.63–4.27). CONCLUSION: The IL36RN mutation is strongly related to GPP without psoriasis vulgaris and the early onset of GPP. Furthermore, the single-nucleotide polymorphism c.115+6T>C of the IL36RN gene plays a significant role in GPP vulnerability, especially in homozygous mutation. GPP could be a different inflammatory disease, independent of psoriasis.