The association between heavy metal and serum cholesterol levels in the US population: National Health and Nutrition Examination Survey 2009–2012

Buhari, Olajide; Dayyab, Farouq Muhammad; Igbinoba, O; Atanda, Adebayo; Medhane, Fitsumberhan; Faillace, Robert T.

doi:10.1177/0960327119889654

Cited by 30 publications

(15 citation statements)

References 24 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GALNT2 plays important roles in lipid homeostasis [ 94 ], and differential methylation of the GALNT2 locus in humans is associated with coronary heart disease [ 95 ], and with sex differences in cardiometabolic diseases [ 96 ]. Interestingly, Pb exposure has been associated in human populations with elevated total and LDL cholesterol [ 97 ], suggesting that Pb may be linked to CVD in part through dysregulation of lipid metabolism. Altered DNA methylation of the GALNT2 locus has also been reported in the blood of infants exposed to maternal smoking [ 98 ], and methylation of this gene in the placenta is associated with cadmium exposure [ 99 ].…”

Section: Discussionmentioning

confidence: 99%

Perinatal Lead Exposure Promotes Sex-Specific Epigenetic Programming of Disease-Relevant Pathways in Mouse Heart

Svoboda

Wang

Goodrich

et al. 2023

Toxics

View full text Add to dashboard Cite

Environmental contaminants such as the metal lead (Pb) are associated with cardiovascular disease, but the underlying molecular mechanisms are poorly understood. In particular, little is known about how exposure to Pb during early development impacts the cardiac epigenome at any point across the life course and potential differences between sexes. In a mouse model of human-relevant perinatal exposures, we utilized RNA-seq and Enhanced Reduced Representation Bisulfite Sequencing (ERRBS) to investigate the effects of Pb exposure during gestation and lactation on gene expression and DNA methylation, respectively, in the hearts of male and female mice at weaning. For ERRBS, we identified differentially methylated CpGs (DMCs) or differentially methylated 1000 bp regions (DMRs) based on a minimum absolute change in methylation of 10% and an FDR < 0.05. For gene expression data, an FDR < 0.05 was considered significant. No individual genes met the FDR cutoff for gene expression; however, we found that Pb exposure leads to significant changes in the expression of gene pathways relevant to cardiovascular development and disease. We further found that Pb promotes sex-specific changes in DNA methylation at hundreds of gene loci (280 DMCs and 99 DMRs in males, 189 DMCs and 121 DMRs in females), and pathway analysis revealed that these CpGs and regions collectively function in embryonic development. In males, differential methylation also occurred at genes related to immune function and metabolism. We then investigated whether genes exhibiting differential methylation at weaning were also differentially methylated in hearts from a cohort of Pb-exposed mice at adulthood. We found that a single gene, Galnt2, showed differential methylation in both sexes and time points. In a human cohort investigating the influence of prenatal Pb exposure on the epigenome, we also observed an inverse association between first trimester Pb concentrations and adolescent blood leukocyte DNA methylation at a locus in GALNT2, suggesting that this gene may represent a biomarker of Pb exposure across species. Together, these data, across two time points in mice and in a human birth cohort study, collectively demonstrate that Pb exposure promotes sex-specific programming of the cardiac epigenome, and provide potential mechanistic insight into how Pb causes cardiovascular disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Perinatal Lead Exposure Promotes Sex-Specific Epigenetic Programming of Disease-Relevant Pathways in Mouse Heart

Svoboda

Wang

Goodrich

et al. 2023

Toxics

View full text Add to dashboard Cite

show abstract

“…Previous epidemiology studies have linked heavy metal exposure to dyslipidemia. In particular, mercuy, lead, arsenic, copper, nickel, and cadmium were reported to be positively associated with serum triglyceride levels ( Buhari et al, 2020 ; Ma et al, 2020 ; Kim et al, 2022 ). In animal studies, cadmium has been evidenced to enhance triglyceride accumulation through reduction of lipoprotein lipase activity ( Barañski et al, 1983 ).…”

Section: Discussionmentioning

confidence: 99%

Association of cerebral spinal fluid copper imbalance in amyotrophic lateral sclerosis

Chen

Wu²,

Wen³

et al. 2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

A plethora of environmental risk factors has been persistently implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), including metal/metalloids. This study aimed to examine potential associations between cerebral spinal fluid (CSF) metal/metalloids and ALS risks. CSF concentrations of copper (Cu), nickel (Ni), mercury (Hg), arsenic (As), manganese (Mn), and iron (Fe) in ALS (spinal- and bulbar-onset) patients and controls were measured using inductively coupled plasma mass spectrometry (ICP-MS). Results from this study revealed marked differences between control, spinal-onset, and bulbar-onset groups. We report that Cu levels were lower in the ALS and spinal-onset groups compared to the control group. Ni level were higher in the spinal-onset group compared to the control and bulbar-onset groups. In addition, associations between CSF metal/metalloid levels with disease severity, sex, and serum triglycerides were also examined to broach the potential relevance of neurotoxic metal/metalloids in ALS disease heterogeneity.

show abstract

“…Endocrine-disrupting chemicals (EDCs) are a diverse class of environmental pollutants with “emerging concern” that interfere with multiple metabolic and hormonal systems in human (Futran Fuhrman et al (2015)). EDCs include pesticides, pharmaceutical agents, toxic metals, plasticizers which are used in many commercial products (Buhari et al (2020)). PFAS are exclusively man-made EDCs and environmentally persistent chemicals which are used to manufacture a wide variety of consumer and industrial products, non-stick, stain and water resistant coatings, fire suppression foams, and cleaning products (Liu et al (2018) and Jain and Ducatman (2018)).…”

Section: Application In Exposure-mixture Association Of Per-and Poly-...mentioning

confidence: 99%

“…Hypercholesterolemia is one of the significant risk factors for CVD and it is characterized by the presence of high levels of cholesterol in the blood. High serum low-density lipoprotein (LDL), total serum cholesterol levels, and low levels of high-density lipoprotein (HDL) in the blood are one of the incriminating factors for the pathogenesis of this disorder (Buhari et al (2020)). Using the theory discussed in the sections above, we aim to quantify the δ -scores of PFAS and metal mixtures on serum lipoprotein-cholesterols and estimate sufficient sample sizes.…”

Section: Application In Exposure-mixture Association Of Pfas and Meta...mentioning

confidence: 99%

Quantifying the Effect Size of Exposure-Outcome Association Using δ-score: Application to Environmental Chemical Mixture studies

Midya

Liao

Gennings

et al. 2022

Preprint

View full text Add to dashboard Cite

In environmental epidemiology, analysis of environmental mixture in association to health effects is gaining popularity. Such models mostly focus on inferences of hypotheses or summarizing strength of association through regression coefficients and corresponding estimates of precision. Nonetheless, when a decision is made against alternative hypothesis, it becomes increasingly difficult to tease apart whether the decision is influenced by sample size or represents genuine absence of association and whether the result warrants further investigation. Similarly, in case of a decision made in favour of alternative hypothesis, a significant association may indicate influence of large sample and not a strong effect. Moreover, the disparate type 1 and type 2 errors, might render these inferences unreliable. Using Cohen’s f2 to evaluate the strength of explanatory associations in a more fundamental way, we herein propose a new concept, optimal impact, to quantify the maximum explanatory association solely contributed by an environmental-mixture after controlling for confounders and covariates such that the type 2 error remains at its minimum. optimal impact is built upon a novel hypothesis testing procedure in which the rejection region is determined in a way that type 1 and type 2 errors are balanced. Even when an association does not achieve statistical significance, its optimal impact might deem it meaningful and strong enough for further investigation. This idea was naturally extended to estimate sample size in designing studies by striking a balance between explanatory precision and utility. The properties of this framework are carefully studied and detailed results are established. A straightforward application of this procedure is illustrated using an exposure-mixture analysis of per-and-poly-fluoroalkyl substances and metals with serum cholesterols using data from 2017–2018 US National Health and Nutrition Examination Survey.

show abstract

The association between heavy metal and serum cholesterol levels in the US population: National Health and Nutrition Examination Survey 2009–2012

Cited by 30 publications

References 24 publications

Perinatal Lead Exposure Promotes Sex-Specific Epigenetic Programming of Disease-Relevant Pathways in Mouse Heart

Perinatal Lead Exposure Promotes Sex-Specific Epigenetic Programming of Disease-Relevant Pathways in Mouse Heart

Association of cerebral spinal fluid copper imbalance in amyotrophic lateral sclerosis

Quantifying the Effect Size of Exposure-Outcome Association Using δ-score: Application to Environmental Chemical Mixture studies

Contact Info

Product

Resources

About