PDF(Pubmed)
Abstract：
UNASSIGNED: Mounting evidence suggests a connection between inflammatory cytokines and adhesive capsulitis (AC). However, the specific systemic inflammatory cytokines contributing to AC have not been clearly identified. This study employed Mendelian randomization (MR) to explore the causal relationships between 41 inflammatory cytokines and AC.
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.
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.
摘要：
■越来越多的证据表明炎症细胞因子和粘连性囊炎（AC）之间存在联系。然而,导致AC的特定全身性炎性细胞因子尚未明确鉴定.这项研究采用孟德尔随机化（MR）来探索41种炎性细胞因子与AC之间的因果关系。
■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。
■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。
