■在掌plant脓疱病(PPP)的发作和过程中观察到循环细胞因子水平的变化;但是,这些变化是由于病因还是次要因素尚不清楚.为了澄清因果关系,我们在本研究中进行了汇总水平的双向孟德尔随机化(MR)分析.
■FinnGen生物库的全基因组关联研究(GWAS)包括212,766名个体(524名PPP患者和212,242名对照)提供了PPP的汇总数据,而与循环细胞因子水平相关的遗传工具变量(IVs)是从14,824个欧洲个体的GWAS中收集的。逆方差加权(IVW),加权中位数(WME),简单模式,和MR-Egger方法用于确定PPP致病细胞因子分类群的变化。敏感性分析,其中包括水平多效性分析,然后进行。采用留一法和MRSteiger检验对结果的可靠性进行了评估,它评估了因果关系的强度。为了评估PPP和循环细胞因子水平之间的反向因果关系,进行了反向MR分析.
■我们的研究表明C-X-C基序趋化因子6(CXCL6)与PPP(比值比,或1.257,95CI:1.001-1.570,p=0.043)。C-C基序趋化因子19(CCL19)和白细胞介素6(IL-6)被认为与PPP的发展具有保护性相关(OR:0.698,95%CI:0.516-0.944,p=0.020;OR:0.656,95CI:0.437-0.985,p=0.042)。经过敏感性和异质性分析,结果稳定。
■在遗传预测水平上,我们确定了导致PPP发生和发展的因果关系相关的炎症相关变量.由于定制的细胞因子治疗,一些难治性PPP的治疗选择已经扩大。为PPP诊断和机制调查产生新的概念。
UNASSIGNED: Variations in circulatory cytokine levels have been observed during the onset and course of palmoplantar pustulosis (PPP); however, whether these changes are due to etiological or secondary factors is unclear. To clarify the causal relationship, we conducted a summarized-level bidirectional Mendelian randomization (MR) analysis in this study.
UNASSIGNED: A FinnGen biobank genome-wide association study (GWAS) of 212,766 individuals (524 PPP patients and 212,242 controls) provided summary data for PPP, whereas genetic instrumental variables (IVs) linked to circulation cytokine levels were gathered from a GWAS of 14,824 European individuals. The inverse-variance weighted (IVW), weighted median (WME), simple mode, and MR-Egger methods were used to ascertain the changes in PPP pathogenic cytokine taxa. Sensitivity analysis, which included horizontal pleiotropy analysis, was then conducted. The reliability of the results was assessed using the leave-one-out approach and the MR Steiger test, which evaluated the strength of a causal relationship. To evaluate the reverse causality between PPP and circulating cytokine levels, a reverse MR analysis was carried out.
UNASSIGNED: Our study demonstrated positive associations between C-X-C motif chemokine 6 (CXCL6) and PPP (odds ratio, OR 1.257, 95%CI: 1.001-1.570, p = 0.043). C-C motif chemokine 19 (CCL19) and interleukin-6 (IL-6) were suggested to be protectively associated with the development of PPP (OR: 0.698,95% CI: 0.516-0.944, p = 0.020; OR: 0.656, 95%CI:0.437-0.985, p = 0.042). The results were steady after sensitivity and heterogeneity analyses.
UNASSIGNED: At the genetic prediction level, we identified causally connected inflammation-related variables that contributed to the onset and development of PPP. The therapeutic options for some refractory PPP have expanded due to tailored cytokine therapy, generating fresh concepts for PPP diagnostics and mechanism investigation.