Shen Yubin, Wang Hongwei, Zhang Weiyu, Ou Xiwen, Liu Song
Department of Respiratory Medicine and Sleep Lab, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People's Republic of China.
Nat Sci Sleep. 2023 Sep 29;15:749-765. doi: 10.2147/NSS.S423331. eCollection 2023.
Obstructive sleep apnea (OSA), high blood pressure (HBP), and type 2 diabetes mellitus (T2DM) have a close clinical relationship, but whether and how OSA affects HBP and T2DM is unclear.
Two-step, two-sample Mendelian randomization techniques were applied using single-nucleotide polymorphisms as genetic instruments for exposure and mediators, thus minimizing bias due to confounding factors and reverse causality. The total effect of OSA on HBP and T2DM was categorized into direct and mediating effects based on the mediating factors.
Two-sample MR analysis showed that OSA increased the risk of HBP (odds ratio [OR] = 1.010, 95% confidence interval [CI], 1.002-1.018; = 0.0121) and T2DM (OR = 1.140, 95% CI, 1.059-1.228; = 0.0005). In the process of OSA caused by HBP, sex hormone-binding globulin (SHBG) (female, 4.47% mediation; male, 2.76% mediation), total testosterone (TT) (male, 3.72% mediation), bioavailable testosterone (BioT) (female, 7.74% mediation), high-density lipoprotein cholesterol (HDL-C) (3.25% mediation), and apolipoprotein A1 (ApoA1) (1.31% mediation) were individual contributors. SHBG (female, 4.10% mediation; male, 1.58% mediation), TT (male, 3.69% mediation), BioT (female, 2.58% mediation), HDL-C (3.32% mediation), ApoA1 (2.14% mediation), and omega-6 fatty acids (2.33% mediation) may have mediating roles to varying degrees in the process of OSA caused by T2DM.
This MR study showed that OSA is a risk factor for HBP and T2DM, and the evaluation of mediators may help further reveal the specific mechanism by which OSA causes HBP and T2DM.
阻塞性睡眠呼吸暂停（OSA）、高血压（HBP）和2型糖尿病（T2DM）存在密切的临床关系，但OSA是否以及如何影响HBP和T2DM尚不清楚。
采用两步两样本孟德尔随机化技术，使用单核苷酸多态性作为暴露和中介因素的遗传工具，从而最大限度地减少混杂因素和反向因果关系导致的偏差。基于中介因素，将OSA对HBP和T2DM的总效应分为直接效应和中介效应。
两样本MR分析显示，OSA增加了HBP（优势比[OR]=1.010，95%置信区间[CI]，1.002 - 1.018；P = 0.0121）和T2DM（OR = 1.140，95%CI，1.059 - 1.228；P = 0.0005）的风险。在HBP导致OSA的过程中，性激素结合球蛋白（SHBG）（女性，中介作用4.47%；男性，中介作用2.76%）、总睾酮（TT）（男性，中介作用3.72%）、生物可利用睾酮（BioT）（女性，中介作用7.74%）、高密度脂蛋白胆固醇（HDL-C）（中介作用3.25%）和载脂蛋白A1（ApoA1）（中介作用1.31%）是个体贡献因素。SHBG（女性，中介作用4.10%；男性，中介作用1.58%）、TT（男性，中介作用3.69%）、BioT（女性，中介作用2.58%）、HDL-C（中介作用3.32%）、ApoA1（中介作用2.14%）和ω-6脂肪酸（中介作用2.33%）在T2DM导致OSA的过程中可能具有不同程度的中介作用。
这项MR研究表明，OSA是HBP和T2DM的危险因素，对中介因素的评估可能有助于进一步揭示OSA导致HBP和T2DM的具体机制。
