背景:已证明代谢紊乱(MetDs)与许多疾病密切相关。然而,MetDs与肺结核(PTB)之间的确切关联尚不清楚.
方法:从BioBank日本项目(BBJ)基因暴露数据集获得来自全基因组关联研究(GWASs)的暴露和结果的汇总统计。14个临床因素分为三组:代谢实验室标志物,血压,以及MetS诊断因素。使用双样本孟德尔随机化(MR)分析代谢因素与PTB之间的因果关系。此外,通过多变量MR研究对PTB风险的直接影响。采用的主要方法是逆方差加权(IVW)模型。使用MR-Egger回归和MR-PRESSO全局检验评估了该MR分析的敏感性。
结果:根据双样本MR,HDL-C,HbA1c,TP,DM与活动性TB的发病率呈正相关。根据多变量MR,HDL-C(IVW:OR2.798,95%CI1.484-5.274,P=0.001),LDL(IVW:OR4.027,95%CI1.140~14.219,P=0.03)和TG(IVW:OR2.548,95%CI1.269~5.115,P=0.009)与PTB的发生呈正相关。TC(OR0.131,95%CI0.028~0.607,P=0.009)与PTB的发生呈负相关。我们选择了BMI,DM,HDL-C,SBP,并将TG作为代谢综合征的诊断因子。DM(IVW,OR1.219,95%CI1.040-1.429P=0.014)和HDL-C(IVW,OR1.380,95%CI1.035-1.841,P=0.028)与PTB的发生直接相关。
结论:这项MR研究表明,代谢紊乱,主要是高血糖,和血脂异常,与活动性肺结核的发病率有关。
BACKGROUND: Metabolic disorders (MetDs) have been demonstrated to be closely linked to numerous diseases. However, the precise association between MetDs and pulmonary tuberculosis (PTB) remains poorly understood.
METHODS: Summary statistics for exposure and outcomes from genome-wide association studies (GWASs) for exposures and outcomes were obtained from the BioBank Japan Project (BBJ) Gene-exposure dataset. The 14 clinical factors were categorized into three groups: metabolic laboratory markers, blood pressure, and the MetS diagnostic factors. The causal relationship between metabolic factors and PTB were analyzed using two-sample Mendelian Randomization (MR). Additionally, the direct effects on the risk of PTB were investigated through multivariable MR. The primary method employed was the inverse variance-weighted (IVW) model. The sensitivity of this MR analysis was evaluated using MR-Egger regression and the MR-PRESSO global test.
RESULTS: According to the two-sample MR, HDL-C, HbA1c, TP, and DM were positively correlated with the incidence of active TB. According to the multivariable MR, HDL-C (IVW: OR 2.798, 95% CI 1.484-5.274, P = 0.001), LDL (IVW: OR 4.027, 95% CI 1.140-14.219, P = 0.03) and TG (IVW: OR 2.548, 95% CI 1.269-5.115, P = 0.009) were positively correlated with the occurrence of PTB. TC (OR 0.131, 95% CI 0.028-0.607, P = 0.009) was negatively correlated with the occurrence of PTB. We selected BMI, DM, HDL-C, SBP, and TG as the diagnostic factors for metabolic syndrome. DM (IVW, OR 1.219, 95% CI 1.040-1.429 P = 0.014) and HDL-C (IVW, OR 1.380, 95% CI 1.035-1.841, P = 0.028) were directly correlated with the occurrence of PTB.
CONCLUSIONS: This MR
study demonstrated that metabolic disorders, mainly hyperglycemia, and dyslipidemia, are associated with the incidence of active pulmonary tuberculosis.