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Metabolomic signatures of lead exposure in the VA Normative Aging Study.

Abstract：

BACKGROUND: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. OBJECTIVES:To identify plasma metabolomic signatures of Pb exposure, as measured in blood and toenails. METHODS: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. RESULTS: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 = 7.18x10-7), N-acetylglycine (β(95%CI): 1.44 (0.85,2.02), p = 1.12x10-6), tartarate (β(95%CI): 0.68 (0.35,1.00), p = 4.84x10-5), vanillylmandelate (β(95%CI): 1.05 (0.47,1.63), p = 4.44x10-7), and lysine (β(95%CI): 1.88 (-2.8,-0.95), p = 9.10x10-5). 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. DISCUSSION: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.

journal_name

Environ Res

journal_title

Environmental research

authors

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

doi

10.1016/j.envres.2020.110022

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

110022

eissn

0013-9351

issn

1096-0953

pii

S0013-9351(20)30919-1

journal_volume

190

pub_type

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Metabolomic signatures of lead exposure in the VA Normative Aging Study.