Abstract：
UNASSIGNED: Psoriasis is a common autoimmune disease in clinical practice, and previous observational studies have suggested that PPARG agonists such as Pioglitazone may be potential therapeutic agents. However, due to interference from various confounding factors, different observational studies have not reached a unified conclusion. We aim to evaluate the potential use of PPARG agonists for treating psoriasis from a new perspective through drug-targeted Mendelian randomization (MR) analysis.
UNASSIGNED: This study includes data on 8,876 individuals for acute myocardial infarction from GWAS, and LDL cholesterol data from 343,621 Europeans. FinnGen contributed psoriasis vulgaris data for 403,972 individuals. The DrugBank10 databases function to identify genes encoding protein products targeted by active constituents of lipid-modifying targets. A two-sample MR analysis and summary-data-based MR (SMR) analysis estimated the associations between expressions of drug target genes and symptoms of psoriasis vulgaris. A multivariable MR study was further conducted to examine if the observed association was direct association.
UNASSIGNED: SMR analysis revealed that enhanced PPARG gene expression in the blood (equivalent to a one standard deviation increase) was a protective factor for psoriasis vulgaris (beta = -0.2017, se = 0.0723, p = 0.0053). Besides, there exists an MR association between LDL mediated by PPARG and psoriasis vulgaris outcomes (beta = -3.9169, se = 0.5676, p = 5.17E-12). These results indicate that PPARG is a therapeutic target for psoriasis, suggesting that psoriasis may be a potential indication for PPARG agonists.
UNASSIGNED: This study confirms that therapeutic activation of PPARG helps suppress the development of psoriasis. Psoriasis may be a new indication for PPARG agonists, such as Pioglitazone. In the future, new anti-psoriatic drugs could be developed targeting PPARG.
UNASSIGNED: This study includes data on 8,876 individuals for acute myocardial infarction from GWAS, and LDL cholesterol data from 343,621 Europeans. FinnGen contributed psoriasis vulgaris data for 403,972 individuals. The DrugBank10 databases function to identify genes encoding protein products targeted by active constituents of lipid-modifying targets. A two-sample MR analysis and summary-data-based MR (SMR) analysis estimated the associations between expressions of drug target genes and symptoms of psoriasis vulgaris. A multivariable MR study was further conducted to examine if the observed association was direct association.
UNASSIGNED: SMR analysis revealed that enhanced PPARG gene expression in the blood (equivalent to a one standard deviation increase) was a protective factor for psoriasis vulgaris (beta = -0.2017, se = 0.0723, p = 0.0053). Besides, there exists an MR association between LDL mediated by PPARG and psoriasis vulgaris outcomes (beta = -3.9169, se = 0.5676, p = 5.17E-12). These results indicate that PPARG is a therapeutic target for psoriasis, suggesting that psoriasis may be a potential indication for PPARG agonists.
UNASSIGNED: This study confirms that therapeutic activation of PPARG helps suppress the development of psoriasis. Psoriasis may be a new indication for PPARG agonists, such as Pioglitazone. In the future, new anti-psoriatic drugs could be developed targeting PPARG.
摘要：
■银屑病是临床上常见的自身免疫性疾病,和以前的观察性研究表明,PPARG激动剂如吡格列酮可能是潜在的治疗药物.然而,由于各种混杂因素的干扰，不同的观测研究没有得出统一的结论。我们旨在通过药物靶向孟德尔随机化（MR）分析，从新的角度评估PPARG激动剂治疗银屑病的潜在用途。
■这项研究包括来自GWAS的8,876名急性心肌梗死患者的数据，和低密度脂蛋白胆固醇数据来自343,621欧洲人。FinnGen提供了403,972名个体的寻常型银屑病数据。DrugBank10数据库的功能是识别编码脂质修饰靶标的活性成分靶向的蛋白质产物的基因。双样本MR分析和基于汇总数据的MR（SMR）分析估计了药物靶基因的表达与寻常型银屑病症状之间的关联。进一步进行多变量MR研究以检查观察到的关联是否是直接关联。
■SMR分析显示，血液中PPARG基因表达增强（相当于一个标准差的增加）是寻常型银屑病的保护因素（β=-0.2017，se=0.0723，p=0.0053）。此外,PPARG介导的LDL与寻常型银屑病结局之间存在MR相关性(β=-3.9169,se=0.5676,p=5.17E-12).这些结果表明，PPARG是银屑病的治疗靶点，提示银屑病可能是PPARG激动剂的潜在指征。
■本研究证实PPARG的治疗性激活有助于抑制银屑病的发展。银屑病可能是PPARG激动剂的新适应症，比如吡格列酮。在未来,可以开发针对PPARG的新的抗银屑病药物。
■这项研究包括来自GWAS的8,876名急性心肌梗死患者的数据，和低密度脂蛋白胆固醇数据来自343,621欧洲人。FinnGen提供了403,972名个体的寻常型银屑病数据。DrugBank10数据库的功能是识别编码脂质修饰靶标的活性成分靶向的蛋白质产物的基因。双样本MR分析和基于汇总数据的MR（SMR）分析估计了药物靶基因的表达与寻常型银屑病症状之间的关联。进一步进行多变量MR研究以检查观察到的关联是否是直接关联。
■SMR分析显示，血液中PPARG基因表达增强（相当于一个标准差的增加）是寻常型银屑病的保护因素（β=-0.2017，se=0.0723，p=0.0053）。此外,PPARG介导的LDL与寻常型银屑病结局之间存在MR相关性(β=-3.9169,se=0.5676,p=5.17E-12).这些结果表明，PPARG是银屑病的治疗靶点，提示银屑病可能是PPARG激动剂的潜在指征。
■本研究证实PPARG的治疗性激活有助于抑制银屑病的发展。银屑病可能是PPARG激动剂的新适应症，比如吡格列酮。在未来,可以开发针对PPARG的新的抗银屑病药物。
