重型痤疮遗传度高、危害患者身心健康，现有研究仅解释了疾病的部分遗传易感性，限制了临床早期诊断及有效治疗。项目组前期利用重型痤疮GWAS数据开展了显著位点间的相互作用分析，发现TP63基因可能是重型痤疮新的易感基因，并发现其蛋白亚型ΔNp63在重型痤疮皮脂腺细胞的表达高于健康对照，但TP63基因在疾病中的作用及机制尚不明确。本项目将在前期基础上，对TP63基因进行外显子及调控区测序，全面搜寻与重型痤疮相关的所有遗传变异；并通过生物信息学分析及多种分子生物学技术，探讨TP63基因及其遗传变异在重型痤疮中的功能及致病机制；分析∆NP63和DDB2蛋白在重型痤疮中的表达相关性及可能的相互作用。通过本研究，明确TP63基因的功能性遗传突变及其蛋白亚型∆NP63的表达是否通过影响皮脂腺细胞增殖活性、角质形成细胞分化凋亡活性及调节炎症因子表达而参与重型痤疮的发生，为重型痤疮早期诊断及靶向治疗奠定理论依据

Severe acne shows high heritability and brings significant harm on patients. But susceptibility genes of severe acne and its functions haven’t been fully understood, which impedes early diagnosis and effective treatment of severe acne. Our previous genome-wide associated study on severe acne and the follow-up gene-gene interactions analysis suggested TP63 is a potential susceptibility gene in severe acne considering its biological implications. And our study show that ΔNp63 protein is up-regulated in lesions form acne patients. However, the role and mechanism that TP63 gene involves in severe acne is not clear. In order to reveal the roles of TP63 in the pathogenesis of severe acne in Chinese Han population, here, we will reveal all the causal variants of TP63 by sequencing its exon and promoter areas. And to explore the biological functions of TP63 and its genetic varies in severe acne by a series of molecular biology techniques. The expression of ∆NP63 & DDB2 protein in severe acne lesions and their functions in disease will also be carried out. This study will provide an enhanced understanding of genetics that will provides the opportunity to build potential new therapeutic strategies and to improve diagnostic and prognostic tests for severe acne.