Blood DNA methylation biomarkers of cumulative lead exposure in adults

Colicino, Elena; Just, Allan C.; Kioumourtzoglou, Marianthi-Anna; Vokonas, Pantel; Sparrow, David; Weisskopf, Marc G.; Nie, Linda H.; Hu, Howard; Schwartz, Joel; Wright, Robert O.; Baccarelli, Andrea A.

doi:10.1038/s41370-019-0183-9

Cited by 35 publications

(25 citation statements)

References 37 publications

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“…In two large population-based PD studies, we used DNAm to estimate cumulative, bone-lead levels by applying an externally developed epigenetic (DNAm) biosensor ( 10 ), and found that PD was strongly associated with the DNAm pattern estimated for tibia-lead levels. Positive associations were seen independently in both studies and persisted after multiple adjustments.…”

Section: Discussionmentioning

confidence: 99%

“…We generated two epigenetic biomarkers for cumulative lead exposure (tibia and patella), developed in the Normative Aging Study (NAS). The epigenetic biosensors of patella and tibia are linear combinations of 59 and 138 CpGs, respectively, identified with site-by-site analysis and combined via machine-learning algorithms trained on K x-ray fluorescence (KXRF) in-vivo measures of bone-lead ( 10 ). To determine lead biomarker levels in SGPD and PEG, we extracted the published regression coefficients from NAS ( 10 ), and applied them to the corresponding DNAm beta matrices.…”

Section: Methodsmentioning

confidence: 99%

“…Recent advances in high-throughput epigenetic technology are paving the way for biomarker discovery in many fields, including exposure science. Two methylation-based biomarkers for cumulative lead exposure measured in the tibia and patella have recently been developed ( 10 ). Using these biomarkers, for the first time we evaluate the influence of methylation-based cumulative lead exposure on PD risk in two, independent population-based studies with over 2600 participants.…”

Section: Introductionmentioning

confidence: 99%

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DNA methylation biomarker for cumulative lead exposure is associated with Parkinson’s disease

et al. 2021

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Lead, a known neurotoxicant, has previously received attention in Parkinson’s disease (PD) research, but epidemiologic studies have been limited in sample size and findings are equivocal. We generated two methylation-based biomarkers for cumulative tibia and patella bone-measured lead exposure in 1528 PD patients and 1169 controls. PD status was associated with increased levels of the DNAm biomarker for tibia-lead levels. We estimated a meta-OR for PD of 1.89 per unit DNAm tibia-lead increase (95% CI 1.59, 2.24; p = 8.1E−13). The current study supports the notion that chronic and long-term lead exposure tracked via DNAm may contribute to PD pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DNA methylation biomarker for cumulative lead exposure is associated with Parkinson’s disease

et al. 2021

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“…There was no control group; each patient acted as their own control. Blood metals or specific biomarkers for cumulative lead exposure (e.g., X-ray fluorescence or whole-blood DNA methylation profiles [ 11 , 24 ]) were also not measured. The number of edetate disodium infusions and the relationship between pre and post edetate disodium urine metal levels were not assessed.…”

Section: Discussionmentioning

confidence: 99%

Urinary Metal Levels after Repeated Edetate Disodium Infusions: Preliminary Findings

Alam

Ujueta

Arenas

et al. 2020

IJERPH

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Environmentally acquired lead and cadmium are associated with increased cardiovascular disease risk. In the Trial to Assess Chelation Therapy, up to 40 infusions with edetate disodium over an approximately one-year period lowered the cardiovascular disease risk in patients with a prior myocardial infarction. We assessed whether a reduction in surrogate measures of total body lead and cadmium, post-edetate disodium urine lead and pre-edetate urine cadmium, could be detected after repeated edetate disodium-based infusions compared to the baseline. Fourteen patients with coronary artery disease received multiple open-label edetate disodium infusions. The urine metals pre- and post-edetate infusion, normalized for urine creatinine, were compared to urine levels pre and post final infusion by a paired t-test. Compared with the pre-edetate values, post-edetate urine lead and cadmium increased by 3581% and 802%, respectively, after the first infusion. Compared to baseline, post-edetate lead decreased by 36% (p = 0.0004). A reduction in post-edetate urine lead was observed in 84% of the patients after the final infusion. Pre-edetate lead decreased by 60% (p = 0.003). Pre-edetate lead excretion became undetectable in nearly 40% of patients. This study suggests that edetate disodium-based infusions may decrease the total body burden of lead. However, our data suggest no significant reduction in the body burden of cadmium.

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“…Adding to the above, increasing the metal intoxication and contaminated environment due to human activities has brought significantly adverse effects on health. Toxic metals such as lead can enter into the body, get deposited in different organs including bone, and cause serious damages [22]. Similarly, low concentrations of aluminium, zinc, chromium, arsenic, copper, nickel, and mercury are also found to be toxic for bone cells and may get accumulated in the bone matrix, causing various diseases [23].…”

Section: Bone Diseasesmentioning

confidence: 99%

Advances in Sensing Technologies for Monitoring of Bone Health

et al. 2020

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Changing lifestyle and food habits are responsible for health problems, especially those related to bone in an aging population. Poor bone health has now become a serious matter of concern for many of us. In order to avoid serious consequences, the early prediction of symptoms and diagnosis of bone diseases have become the need of the hour. From this inspiration, the evolution of different bone health monitoring techniques and measurement methods practiced by researchers and healthcare companies has been discussed. This paper focuses on various types of bone diseases along with the modeling and remodeling phenomena of bones. The evolution of various diagnosis tests for bone health monitoring has been also discussed. Various types of bone turnover markers, their assessment techniques, and recent developments for the monitoring of biochemical markers to diagnose the bone conditions are highlighted. Then, the paper focuses on the potential assessment of the recent sensing techniques (physical sensors and biosensors) that are currently available for bone health monitoring. Considering the importance of electrochemical biosensors in terms of high sensitivity and reliability, specific attention has been given to the recent development of electrochemical biosensors and significance in real-time monitoring of bone health.

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Blood DNA methylation biomarkers of cumulative lead exposure in adults

Cited by 35 publications

References 37 publications

DNA methylation biomarker for cumulative lead exposure is associated with Parkinson’s disease

DNA methylation biomarker for cumulative lead exposure is associated with Parkinson’s disease

Urinary Metal Levels after Repeated Edetate Disodium Infusions: Preliminary Findings

Advances in Sensing Technologies for Monitoring of Bone Health

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