Variants in PRKCE and KLC1, Potential Regulators of Type I Psoriasis

Jianxiao Xing,1 Ying Wang,1 Xincheng Zhao,1 Junqin Li,1 Ruixia Hou,1 Xuping Niu,1 Guohua Yin,1 Xinhua Li,1 Kaiming Zhang2 1Shanxi Key Laboratory of Stem Cell for Immunological Dermatosis, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, 030009, Shanxi Province, People’s Republic of China; 2Shanxi Key Laboratory of Stem Cell for Immunological Dermatosis, Taiyuan Central Hospital, Taiyuan, 030009, Shanxi Province, People’s Republic of ChinaCorrespondence: Kaiming Zhang, Taiyuan Central Hospital, No, 5 Dong San Dao Xiang, Jiefang Road, Taiyuan, Shanxi Province, People’s Republic of China, Tel +86-0351-5656080, Email zhangkaiming@sina.comPurpose: Psoriasis is a multifactorial disease with a complex genetic predisposition. The pathophysiology of psoriasis is associated with genetic variants. To better characterize gene variants in psoriasis and identify the relationship between clinical characteristics and variant genes in its pathogenesis.Patients and Methods: DNA was extracted and purified from eight pairs of monozygotic twins with psoriasis discordance and 282 type I psoriasis patients. Thirteen variable genes were amplified and sequenced using the Sanger method after whole genome sequencing.Results: Thirteen genes were found to be variable in eight pairs of monozygotic twins with psoriasis discordance. Among the 13 genes, the variant frequencies of protein kinase C epsilon (PRKCE) (c.240T>C, 35.9% vs 47.7%, P < 0.05) and kinesin light chain 1 (KLC1) (c.216A>G, 2.9% vs 98.1%, P< 0.01) were significantly lower in psoriasis than in normal Asian individuals. Additionally, we found considerable differences in the relationship between variants in genes CADM2, JPH2, SPTLC3 and clinical characteristics stratified by medical history and family history. Moreover, the variants in MEGF6 (39.52% vs 22.50%, χ2=3.83, p < 0.05) showed a stronger association with the mild group (PASI ≤ 10) than the heavy group.Conclusion: Our results provide a comprehensive correlation analysis of regulatory genes that are regulated in psoriasis. This integrated analysis offers novel insight into the pathogenic mechanisms involved in psoriasis.Graphical Abstract: Keywords: psoriasis, gene variants, PRKCE, KLC1