血线粒体 DNA 拷贝数（mtDNA-CN）与哮喘风险、严重程度及急性发作的关系
2025/06/16
摘要：
背景：哮喘的病理生理学机制与线粒体功能障碍相关。线粒体DNA拷贝数（mtDNA-CN）作为线粒体功能的替代指标，已有心血管疾病和癌症相关研究表明其水平降低提示线粒体功能障碍。
目的：探讨mtDNA-CN水平降低是否与哮喘诊断、严重程度及急性发作相关。
方法：通过两个队列血液样本评估mtDNA-CN：英国生物银行（UKB）（哮喘患者n=39,147；非哮喘者n=302,302）和重症哮喘研究计划（SARP）（哮喘患者n=1,283；非重症哮喘n=703）。
结果：UKB队列中哮喘患者的mtDNA-CN显著低于非哮喘组（β=-0.006[95%CI:-0.008至-0.003]，P=6.23×10-6）。较低mtDNA-CN与哮喘患病率相关，但在UKB或SARP中均未显示与疾病严重程度相关。mtDNA-CN随年龄增长而下降，但各年龄段哮喘患者的mtDNA-CN均低于非哮喘者。SARP为期1年的纵向研究显示，mtDNA-CN与急性发作风险相关—最高mtDNA-CN组患者的急性发作风险最低（OR=0.333[95%CI:0.173-0.542]，P=0.001）。哮喘患者的炎症和氧化应激生物标志物水平虽高于非哮喘者，但其mtDNA-CN降低与全身性炎症或氧化应激无关。孟德尔随机化研究表明，哮喘相关遗传变异与mtDNA-CN可能存在因果关系。
结论：哮喘患者的mtDNA-CN水平降低，且与急性发作相关。哮喘患者mtDNA-CN降低并非由炎症介导，而与哮喘遗传易感性相关。
关键词：线粒体DNA；哮喘；急性发作。
文献来源：（Xu W, Hong YS, Hu B, et al. Mitochondrial DNA copy number variation in asthma risk, severity, and exacerbations. J Allergy Clin Immunol. 2025;155(4):1224-1235. doi:10.1016/j.jaci.2024.08.022）
Background:Asthma pathophysiology is associated with mitochondrial dysfunction. Mitochondrial DNA copy number (mtDNA-CN) has been used as a proxy of mitochondrial function, with lower levels indicating mitochondrial dysfunction in population studies of cardiovascular diseases and cancers.
Objectives:We investigated whether lower levels of mtDNA-CN are associated with asthma diagnosis, severity, and exacerbations.
Methods:mtDNA-CN is evaluated in blood from 2 cohorts: UK Biobank (UKB) (asthma, n = 39,147; no asthma, n = 302,302) and Severe Asthma Research Program (SARP) (asthma, n = 1283; nonsevere asthma, n = 703).
Results:Individuals with asthma have lower mtDNA-CN compared to individuals without asthma in UKB (beta, -0.006 [95% confidence interval, -0.008 to -0.003], P = 6.23 × 10-6). Lower mtDNA-CN is associated with asthma prevalence, but not severity in UKB or SARP. mtDNA-CN declines with age but is lower in individuals with asthma than in individuals without asthma at all ages. In a 1-year longitudinal study in SARP, mtDNA-CN was associated with risk of exacerbation; those with highest mtDNA-CN had the lowest risk of exacerbation (odds ratio 0.333 [95% confidence interval, 0.173 to 0.542], P = .001). Biomarkers of inflammation and oxidative stress are higher in individuals with asthma than without asthma, but the lower mtDNA-CN in asthma is independent of general inflammation or oxidative stress. Mendelian randomization studies suggest a potential causal relationship between asthma-associated genetic variants and mtDNA-CN.
Conclusion:mtDNA-CN is lower in asthma than in no asthma and is associated with exacerbations. Low mtDNA-CN in asthma is not mediated through inflammation but is associated with a genetic predisposition to asthma.
Keywords: Mitochondrial DNA; asthma; exacerbations.
背景：哮喘的病理生理学机制与线粒体功能障碍相关。线粒体DNA拷贝数（mtDNA-CN）作为线粒体功能的替代指标，已有心血管疾病和癌症相关研究表明其水平降低提示线粒体功能障碍。
目的：探讨mtDNA-CN水平降低是否与哮喘诊断、严重程度及急性发作相关。
方法：通过两个队列血液样本评估mtDNA-CN：英国生物银行（UKB）（哮喘患者n=39,147；非哮喘者n=302,302）和重症哮喘研究计划（SARP）（哮喘患者n=1,283；非重症哮喘n=703）。
结果：UKB队列中哮喘患者的mtDNA-CN显著低于非哮喘组（β=-0.006[95%CI:-0.008至-0.003]，P=6.23×10-6）。较低mtDNA-CN与哮喘患病率相关，但在UKB或SARP中均未显示与疾病严重程度相关。mtDNA-CN随年龄增长而下降，但各年龄段哮喘患者的mtDNA-CN均低于非哮喘者。SARP为期1年的纵向研究显示，mtDNA-CN与急性发作风险相关—最高mtDNA-CN组患者的急性发作风险最低（OR=0.333[95%CI:0.173-0.542]，P=0.001）。哮喘患者的炎症和氧化应激生物标志物水平虽高于非哮喘者，但其mtDNA-CN降低与全身性炎症或氧化应激无关。孟德尔随机化研究表明，哮喘相关遗传变异与mtDNA-CN可能存在因果关系。
结论：哮喘患者的mtDNA-CN水平降低，且与急性发作相关。哮喘患者mtDNA-CN降低并非由炎症介导，而与哮喘遗传易感性相关。
关键词：线粒体DNA；哮喘；急性发作。
文献来源：（Xu W, Hong YS, Hu B, et al. Mitochondrial DNA copy number variation in asthma risk, severity, and exacerbations. J Allergy Clin Immunol. 2025;155(4):1224-1235. doi:10.1016/j.jaci.2024.08.022）
（ 南方医科大学南方医院 彭晓阡 羊洁 赵海金）
AbstractBackground:Asthma pathophysiology is associated with mitochondrial dysfunction. Mitochondrial DNA copy number (mtDNA-CN) has been used as a proxy of mitochondrial function, with lower levels indicating mitochondrial dysfunction in population studies of cardiovascular diseases and cancers.
Objectives:We investigated whether lower levels of mtDNA-CN are associated with asthma diagnosis, severity, and exacerbations.
Methods:mtDNA-CN is evaluated in blood from 2 cohorts: UK Biobank (UKB) (asthma, n = 39,147; no asthma, n = 302,302) and Severe Asthma Research Program (SARP) (asthma, n = 1283; nonsevere asthma, n = 703).
Results:Individuals with asthma have lower mtDNA-CN compared to individuals without asthma in UKB (beta, -0.006 [95% confidence interval, -0.008 to -0.003], P = 6.23 × 10-6). Lower mtDNA-CN is associated with asthma prevalence, but not severity in UKB or SARP. mtDNA-CN declines with age but is lower in individuals with asthma than in individuals without asthma at all ages. In a 1-year longitudinal study in SARP, mtDNA-CN was associated with risk of exacerbation; those with highest mtDNA-CN had the lowest risk of exacerbation (odds ratio 0.333 [95% confidence interval, 0.173 to 0.542], P = .001). Biomarkers of inflammation and oxidative stress are higher in individuals with asthma than without asthma, but the lower mtDNA-CN in asthma is independent of general inflammation or oxidative stress. Mendelian randomization studies suggest a potential causal relationship between asthma-associated genetic variants and mtDNA-CN.
Conclusion:mtDNA-CN is lower in asthma than in no asthma and is associated with exacerbations. Low mtDNA-CN in asthma is not mediated through inflammation but is associated with a genetic predisposition to asthma.
Keywords: Mitochondrial DNA; asthma; exacerbations.
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