UNASSIGNED: In this bidirectional, two-sample MR analysis, genetic variations associated with AC were derived from a comprehensive genome-wide association study (GWAS). The inflammatory cytokines data were sourced from a GWAS summary involving 8,293 healthy participants. The primary MR method employed was inverse variance weighting, supplemented by MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier for sensitivity analysis. Heterogeneity was assessed using Cochran\'s Q test, and the MR results were validated using the leave-one-out method.
UNASSIGNED: Elevated levels of interferon gamma-induced protein 10 (IP-10) (odds ratio (OR) = 1.086, 95% confidence interval (CI) = 1.002-1.178) and regulated on activation, normal T cell expressed and secreted (RANTES) (OR = 1.107, 95% CI = 1.026-1.195) were linked to an increased risk of AC. Increased levels of stromal cell-derived factor-1 alpha (SDF-1α) (OR = 0.879, 95% CI = 0.793-0.974) and tumor necrosis factor-alpha (TNF-α) (OR = 0.911, 95% CI = 0.831-0.999) were associated with a reduced AC risk. Moreover, genetically predicted AC exhibited associations with elevated cutaneous T cell attracting (CTACK) levels (OR = 1.202, 95% CI = 1.007-1.435) and diminished levels of interleukin-17 (IL-17) (OR = 0.678, 95% CI = 0.518-0.888) and interleukin-5 (IL-5) (OR = 0.786, 95% CI = 0.654-0.944), as confirmed through inverse-variance weighted (IVW) methods.
UNASSIGNED: The present study successfully establishes a causal association between genetically proxied circulating levels of IP-10, RANTES, SDF-1α, and TNF-α and the risk of AC. Additionally, AC contributes to an increase in CTACK and a decrease in IL-17 and IL-5. This significant finding not only enhances the understanding of the pathogenesis of AC but also holds promise for the development of effective clinical management strategies.
■在这种双向双样本MR分析,与AC相关的遗传变异来自一项全面的全基因组关联研究(GWAS).炎性细胞因子数据来自涉及8,293名健康参与者的GWAS摘要。采用的主要MR方法是方差逆加权,由MR-Egger补充,加权中位数,和MR多效性残差和异常值进行敏感性分析。异质性使用Cochran的Q检验进行评估,并使用留一法验证MR结果。
■干扰素γ诱导蛋白10(IP-10)水平升高(比值比(OR)=1.086,95%置信区间(CI)=1.002-1.178),并在激活时受到调节,正常T细胞表达和分泌(RANTES)(OR=1.107,95%CI=1.026-1.195)与AC风险增加有关。基质细胞衍生因子-1α(SDF-1α)(OR=0.879,95%CI=0.793-0.974)和肿瘤坏死因子-α(TNF-α)(OR=0.911,95%CI=0.831-0.999)水平升高与AC风险降低相关。此外,遗传预测的AC表现出与皮肤T细胞吸引(CTACK)水平升高(OR=1.202,95%CI=1.007-1.435)和白细胞介素17(IL-17)水平降低(OR=0.678,95%CI=0.518-0.888)和白细胞介素5(IL-5)(OR=0.786,95%CI=0.654-0.944)相关,通过逆方差加权(IVW)方法证实。
■本研究成功地建立了IP-10,RANTES,SDF-1α,TNF-α和AC的风险。此外,AC有助于CTACK的增加和IL-17和IL-5的减少。这一重要发现不仅增强了对AC发病机理的理解,而且为制定有效的临床管理策略提供了希望。