首页|循环炎症因子与PCOS风险之间的关联评估:一项双样本孟德尔随机化研究

循环炎症因子与PCOS风险之间的关联评估:一项双样本孟德尔随机化研究

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目的 采用孟德尔随机化(MR)方法来探究在遗传水平上循环炎症因子与多囊卵巢综合征(PCOS)的关联性。方法 从SCALLOP联盟数据库(https://www。phpc。cam。ac。uk/ceu/proteins)中获取循环炎症因子的GW AS数据集,筛选符合条件的单核苷酸多态性(SNP)作为暴露变量,从Finngen数据库(r9。finngen。fi/pheno/E4_PCOS)中提取与PCOS相关的SNP用作结局变量,进行MR研究,采用逆方差加权法(IVW)作为该研究评估因果效应的主要分析方法,并以MR-Egger回归法、加权中位数法(WME)、基于众数的加权估计(WM)、基于众数的简单估计(SM)等作为补充方法,并通过Cochran'Q检验、MR-Egger回归的截距等进行敏感性分析。结果 IVW结果表明,在遗传水平上,欧洲人群中白细胞介素-18(IL-18)、IL-6、基质金属蛋白酶-10(MMP-10)、γ-干扰素(IFN-γ)等循环炎症因子与PCOS患病风险之间存在关联性,其中IL-18[OR=1。255,95%CI(1。002,1。572),P=0。048],IL-6[OR=1。434,95%CI(1。025,2。008),P=0。036]以及 MMP-10[OR=1。338,95%CI(1。058,1。693),P=0。015]会增加 PCOS 患病风险,而 IFN-γ[OR=0。631,95%CI(0。441,0。902),P=0。012]则会降低PCOS患病风险;同时,敏感性分析未发现存在异质性以及多效性(P>0。05),表明研究结果没有产生偏倚,留一法结果也提示结果稳健。结论 在欧洲人群基因水平上,IL-18、IL-6及MMP-10循环炎症因子与PCOS患病率的风险升高存在相关性,IFN-γ与PCOS患病率风险下降存在相关性。
Association between circulating inflammatory factors and the risk of PCOS:A two-sample Mendelian randomized study
Objective:To explore the association of circulating inflammatory factors with PCOS at the genetic level with Mendelian randomization(MR).Methods:A genome-wide association study(GW AS)dataset of circulating inflammatory factors was obtained from the SCALLOP consortium database(https://www.phpc.cam.ac.uk/ceu/proteins)to screen for eligible single nucleotide polymorphisms(SNPs)as exposure variables,and SNPs associated with PCOS were obtained from the Finngen database(r9.finngen.fi/pheno/E4_PCOS)to use as endpoints for MR studies.We used inverse variance weighting(IVW)for the main analysis to assess the causal effect,with the MR-Egger method,weighted median method(WME),weighted mode(WM),and simple mode(SM)for supplementary causal analyses.The Cochran'Q test and MR-Egger intercept test were used for sensitivity analysis.Results:The IVW results showed an association between circulating inflammatory factors including interleukin(IL)-18,IL-6,matrix metalloproteinases(MMP)-10,interferon(IFN)-γ and the risk of developing PCOS at the genetic level in a European population.IL-18[OR=1.255,95%CI(1.002,1.572),P=0.048],IL-6[OR=1.434,95%CI(1.025,2.008),P=0.036]and MMP-10[OR=1.338,95%CI(1.058,1.693),P=0.015]were positively correlated with the prevalence of PCOS,and IFN-γ[OR=0.631,95%CI(0.441,0.902),P=0.012]was negatively correlated with the incidence of PCOS.The sensitivity analysis detected no heterogeneity or horizontal pleiotropy(P>0.05),which indicated no bias in the results.The leave-one-out analysis suggested that the results were robust.Conclusions:The results of our analyses showed a correlation between the circulating inflammatory factors including IL-18,IL-6,and MMP-10 and an increased risk of PCOS prevalence,and a correlation between IFN-γ and a decreased risk of PCOS prevalence at the gene level in a European population.

PCOSCirculating inflammatory factorMendelian randomization study

袁山政、张燕雨、翟亚悦、张增、李泽琳、廖莎、高宁、郑伟、徐慧军

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山东中医药大学,济南 250014

青岛市第五人民医院,青岛 266002

青岛市中医医院,青岛 266000

多囊卵巢综合征 循环炎症因子 孟德尔随机化研究

山东省中医药科技项目

M-2022017

2024

生殖医学杂志
北京协和医院 国家人口计生委科学技术研究所

生殖医学杂志

CSTPCD
影响因子:1.24
ISSN:1004-3845
年,卷(期):2024.33(9)