Metabolomic signatures of lead exposure in the VA Normative Aging Study.
Metabolomic signatures of lead exposure in the VA Normative Aging Study.
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DOI：
10.1016/j.envres.2020.110022
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发表时间：
2020-11
影响因子：
8.3
通讯作者：
Lasky-Su JA
中科院分区：
文献类型：
--
作者：
Kelly RS;Bayne H;Spiro A 2nd;Vokonas P;Sparrow D;Weiss ST;Schwartz J;Nassan FL;Lee-Sarwar K;Huang M;Kachroo P;Chu SH;Litonjua AA;Lasky-Su JA
铅（Pb）广泛存在，接触这种非必需重金属会对健康造成多重负面影响；然而，这些影响背后的机制仍然不完全清楚。鉴定血和脚趾甲中铅暴露的血浆代谢组学特征。在VA规范衰老研究的一组男性中，进行了基于质谱的血浆代谢组学分析。同时采集血液样本和脚趾甲剪报，测量铅水平。采用多变量线性回归模型、平滑样条和Pathway分析来鉴定与铅暴露相关的代谢物。在399名男性中，858项代谢物检测通过QC，其中154项（17.9%）与血铅显著相关（p < 0.05）。其中11种通过了严格的多重检验校正，包括原羟基pro (β(95%CI): 1.52 (0.93,2.12), p = 7.18×10−7)，n -乙酰甘氨酸(β(95%CI): 1.44 (0.85,2.02), p = 1.12×10−6)，酒石酸盐(β(95%CI): 0.68 (0.35,1.00), p = 4.84×10−5)，香草酸盐(β(95%CI): 1.05 (0.47,1.63), p = 4.44×10−7)，赖氨酸(β（95%CI): 1.88 (- 2.8, - 0.95), p = 9.10×10−5）。48名男性的一个子集在第一次采集血液样本的平均6.1年后采集了第二次血液样本。前11种代谢物中的3种在第二份血液样本中也很显著。此外，我们在脚趾甲中鉴定了70种与铅相关的血浆代谢物。23种血浆代谢物与血液和脚趾甲测量值显著相关，而其他代谢物似乎与测量铅的生物样本特异性相关。例如，苯甲酸盐代谢似乎对通过脚趾甲评估的长期暴露具有重要意义。铅暴露占全球疾病负担的0.6%，代谢组学特别适合探索其致病机制。在这项研究中，我们确定了与铅暴露相关的代谢物和代谢组学途径，表明铅暴露通过氧化应激和免疫功能障碍起作用。这些发现有助于我们更好地了解这一重要公共卫生负担的生物学。
Lead (Pb) is widespread and exposure to this non-essential heavy metal can cause multiple negative health effects; however the mechanisms underlying these effects remain incompletely understood. To identify plasma metabolomic signatures of Pb exposure, as measured in blood and toenails. In a subset of men from the VA Normative Aging Study, mass-spectrometry based plasma metabolomic profiling was performed. Pb levels were measured in blood samples and toenail clippings collected concurrently. Multivariable linear regression models, smoothing splines and Pathway analyses were employed to identify metabolites associated with Pb exposure. In 399 men, 858 metabolites were measured and passed QC, of which 154 (17.9%) were significantly associated with blood Pb (p < 0.05). Eleven of these passed stringent correction for multiple testing, including pro-hydroxy-pro (β(95%CI): 1.52 (0.93,2.12), p = 7.18×10−7), N-acetylglycine (β(95%CI): 1.44 (0.85,2.02), p = 1.12×10−6), tartarate (β(95%CI): 0.68 (0.35,1.00), p = 4.84×10−5), vanillylmandelate (β(95%CI): 1.05 (0.47,1.63), p = 4.44×10−7), and lysine (β(95%CI): 1.88 (−2.8,−0.95), p = 9.10×10−5). A subset of 48 men had a second blood sample collected a mean of 6.1 years after their first. Three of the top eleven metabolites were also significant in this second blood sample. Furthermore, we identified 70 plasma metabolites associated with Pb as measured in toenails. Twenty-three plasma metabolites were significantly associated with both blood and toenail measures, while others appeared to be specific to the biosample in which Pb was measured. For example, benzanoate metabolism appeared to be of importance with the longer-term exposure assessed by toenails. Pb exposure is responsible for 0.6% of the global burden of disease and metabolomics is particularly well-suited to explore its pathogenic mechanisms. In this study, we identified metabolites and metabolomic pathways associated with Pb exposure that suggest that Pb exposure acts through oxidative stress and immune dysfunction. These findings help us to better understand the biology of this important public health burden.
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影响因子：
3.7
作者：
Kelly RS;Lundh T;Porta M;Bergdahl IA;Palli D;Johansson AS;Botsivali M;Vineis P;Vermeulen R;Kyrtopoulos SA;Chadeau-Hyam M;EnviroGenoMarkersProject Consortium
通讯作者：
EnviroGenoMarkersProject Consortium
影响因子：
5.3
作者：
Li MX;Yeung JM;Cherny SS;Sham PC
通讯作者：
Sham PC
影响因子：
10.4
作者：
Bakulski KM;Park SK;Weisskopf MG;Tucker KL;Sparrow D;Spiro A 3rd;Vokonas PS;Nie LH;Hu H;Weuve J
通讯作者：
Weuve J
DOI：
10.1007/bf00517950
发表时间：
1993-02-01
影响因子：
3
作者：
FAR, HS;PIN, NT;YAN, CK
通讯作者：
YAN, CK
影响因子：
9.6
作者：
Kelly, Rachel S.;Chawes, Bo L.;Lasky-Su, Jessica A.
通讯作者：
Lasky-Su, Jessica A.