Mitochondria-derived methylmalonic acid, a surrogate biomarker of mitochondrial dysfunction and oxidative stress, predicts all-cause and cardiovascular mortality in the general population.
Mitochondria-derived methylmalonic acid, a surrogate biomarker of mitochondrial dysfunction and oxidative stress, predicts all-cause and cardiovascular mortality in the general population.
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线粒体衍生的甲基丙二酸是线粒体功能障碍和氧化应激的替代生物标志物，可预测普通人群的全因死亡率和心血管死亡率
DOI：
10.1016/j.redox.2020.101741
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发表时间：
2020-10
期刊：
影响因子：
11.4
通讯作者：
Yu B
中科院分区：
文献类型：
--
作者：
Wang S;Liu Y;Liu J;Tian W;Zhang X;Cai H;Fang S;Yu B
遗传性甲基丙二酸血症的特点是线粒体功能障碍，氧化应激，并损害富含维生素A的器官在儿童。目前还不清楚甲基丙二酸（MMA）是否与成人的不良预后有关。该研究旨在调查MMA与一般人群中全因和特定原因死亡率的关系。总体而言，来自美国国家健康和营养检查调查（NHANES）的23，437名成年人入组。NHANES 1999-2004和2011-2014分别用作主要和验证子集（中位随访时间分别为13.5和2.8年）。用气相色谱/质谱法测定循环MMA。使用加权考克斯回归模型估计风险比（HR）。在1999-2004年NHANES的163，632人-年随访期间，发生了3019例死亡。在多变量校正模型中，与MMA <120 nmol/L的受试者相比，MMA≥250 nmol/L的受试者的全因和心血管死亡率增加[HR（95%CI）分别为1.62（1.43-1.84）和1.66（1.22-2.27）]。这种关联在服用正常钴胺素的参与者中尤为显著。MMA仍然是5年、5-10年或超过10年随访期内发生的全因死亡率的独立预测因素（趋势的每个p ≤0.007）。这种关联在2011-2014年的NHANES中重复出现。此外，基线MMA改善了心血管疾病患者10年死亡率的重新分类（净重新分类指数为0.239，综合区分改善为0.022），优于已建立的心血管生物标志物C反应蛋白或同型半胱氨酸。血液中MMA的循环水平与全因死亡率和心血管死亡率的升高密切相关。我们的研究结果支持MMA作为线粒体功能障碍的替代生物标志物来预测成人的不良预后。心血管疾病的生物学机制值得进一步研究。MMA与线粒体氧化应激和儿童富含维生素A的器官损伤有关。这项研究提供了第一个证据表明MMA与成人的总死亡率和心血管死亡率密切相关。这种联系对于功能性钴胺素缺乏症的参与者更强，这与氧化还原失衡有关。MMA改善心血管疾病患者的危险分层优于同型半胱氨酸和C反应蛋白。
Inherited methylmalonic acidemia is characterized by mitochondrial dysfunction, oxidative stress, and damage of mitochondria-rich organs in children. It is unclear whether methylmalonic acid (MMA) is related to poor prognosis in adults. The study aims to investigate the associations of MMA with all-cause and cause-specific mortality in the general population. Overall, 23,437 adults from the US National Health and Nutrition Examination Survey (NHANES) were enrolled. NHANES 1999–2004 and 2011–2014 were separately used as primary and validation subsets (median follow-up 13.5 and 2.8 years, respectively). Circulating MMA was measured with gas chromatography/mass spectrophotometry. Hazard ratios (HR) were estimated using weighted Cox regression models. During 163,632 person-years of follow-up in NHANES 1999–2004, 3019 deaths occurred. Compared with participants with MMA <120 nmol/L, those with MMA≥250 nmol/L had increased all-cause and cardiovascular mortality in the multivariable-adjusted model [HR(95%CI), 1.62 (1.43–1.84) and 1.66 (1.22–2.27), respectively]. The association was especially significant among participants with normal cobalamin. MMA remained an independent predictor of all-cause mortality occurring whether within 5-year, 5–10 years, or beyond 10-year of follow-up (each p for trend≤0.007). That association was repeatable in NHANES 2011–2014. Moreover, baseline MMA improved reclassification for 10-year mortality in patients with cardiovascular disease (net reclassification index 0.239, integrated discrimination improvement 0.022), overmatched established cardiovascular biomarkers C-reactive protein or homocysteine. Circulating level of mitochondrial-derived MMA is strongly associated with elevated all-cause and cardiovascular mortality. Our results support MMA as a surrogate biomarker of mitochondrial dysfunction to predict poor prognosis in adults. The biological mechanisms under cardiovascular disease warrant further investigation. MMA has been implicated in mitochondrial oxidation stress, and the damage of mitochondria-rich organs in children. This study provides the first evidence that MMA is robustly associated with total and cardiovascular mortality in adults. This link is stronger for participants with functional cobalamin deficiency which has been linked with redox imbalance. MMA improves risk stratification in patients with cardiovascular disease outmatched homocysteine and C-reactive protein.
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影响因子：
7.4
作者：
Mesaros, Clementina;Arora, Jasbir S.;Wholer, Ashley;Vachani, Anil;Blair, Ian A.
通讯作者：
Blair, Ian A.
DOI：
10.1016/j.hlc.2018.03.007
发表时间：
2019-04
期刊：
Heart, lung & circulation
影响因子：
--
作者：
Kubota Y;Alonso A;Heckbert SR;Norby FL;Folsom AR
通讯作者：
Folsom AR
影响因子：
3
作者：
Melo, Daniela R.;Kowaltowski, Alicia J.;Castilho, Roger F.
通讯作者：
Castilho, Roger F.
DOI：
10.1073/pnas.1302764110
发表时间：
2013-08-13
影响因子：
11.1
作者：
Manoli, Irini;Sysol, Justin R.;Venditti, Charles P.
通讯作者：
Venditti, Charles P.
影响因子：
37.8
作者：
Peters, Sanne A. E.;Muntner, Paul;Woodward, Mark
通讯作者：
Woodward, Mark