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Abstract：
Psoriasis vulgaris (PV) and Atopic dermatitis (AD) are the two major types of immune-mediated inflammatory skin disease (IMISD). Limited studies reported the association between Ubiquitin-conjugating enzyme E2 (UBE2) and IMISD. We employed a two-sample Mendelian randomization (MR) study to assess the causality between UBE2 and PV & AD. UBE2 association genome-wide association study (GWAS) data were collected. The inverse variance weighted (IVW) method was utilized as the principal method in our Mendelian randomization (MR) study, with additional using the MR-Egger, weighted median, simple mode, and weighted mode methods. The MR-Egger intercept test, Cochran\'s Q test, MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and leave-one-out analysis were conducted to identify heterogeneity and pleiotropy, colocalization analysis was also performed. The results showed that Ubiquitin-conjugating enzyme E2 variant 1 (UBE2V1) was causally associated with PV (OR = 0.909, 95% CI: 0.830-0.996, P = 0.040), Ubiquitin-conjugating enzyme E2 L3 (UBE2L3) was causally associated with AD (OR = 0.799, 95% CI: 0.709-0.990, P < 0.001). Both UBE2V1 and UBE2L3 may play protective roles in patients with PV or AD, respectively. No other significant result has been investigated. No heterogeneity or pleiotropy was observed. This study provided new evidence of the relationship between UBE2V1 and PV, UBE2L3 and AD. Our MR suggested that UBE2V1 plays an inhibitory role in PV progression, UBE2L3 plays an inhibitory role in AD. These could be novel and effective ways to treat PV and AD.
摘要：
寻常型银屑病(PV)和特应性皮炎(AD)是免疫介导的炎症性皮肤病(IMISD)的两种主要类型。有限的研究报道了泛素结合酶E2（UBE2）与IMISD之间的关联。我们采用双样本孟德尔随机化（MR）研究来评估UBE2与PV和AD之间的因果关系。收集UBE2关联全基因组关联研究(GWAS)数据。在我们的孟德尔随机化(MR)研究中，方差逆加权(IVW)方法被用作主要方法，额外使用MR-Egger，加权中位数，简单模式，和加权模式方法。MR-Egger截距测试,Cochran的Q测试,进行MR-PleiotropicRESidualSumand离群值(MR-PRESSO)和留一法分析以确定异质性和多效性。还进行了共定位分析.结果表明，泛素结合酶E2变体1（UBE2V1）与PV有因果关系（OR=0.909，95％CI：0.830-0.996，P=0.040）。泛素结合酶E2L3(UBE2L3)与AD有因果关系(OR=0.799,95%CI:0.709-0.990,P<0.001)。UBE2V1和UBE2L3可能在PV或AD患者中发挥保护作用。分别。没有调查其他重要结果。没有观察到异质性或多效性。本研究为UBE2V1与PV之间的关系提供了新的证据，UBE2L3和AD。我们的MR提示UBE2V1在PV进展中起抑制作用，UBE2L3在AD中起抑制作用。这些可能是治疗PV和AD的新的有效方法。
