In silico epigenetics of metal exposure and subclinical atherosclerosis in middle aged men: Pilot results from the aragon workers health study

Angela L. Riffo-Campos, Azahara Fuentes-Trillo, Wan-Yee Tang, Zoraida Soriano, Griselda De Marco, Pilar Rentero-Garrido, Victoria Adam-Felici, Veronica Lendinez-Tortajada, Kevin Francesconi, Walter Goessler, Christine Marie Ladd-Acosta, Montse Leon-Latre, Jose A. Casasnovas, F. Javier Chaves, Ana Navas Acien, Eliseo Guallar, Maria Tellez-Plaza

Research output: Contribution to journalArticle

Abstract

We explored the association of metal levels with subclinical atherosclerosis and epigenetic changes in relevant biological pathways. Whole blood DNA Infinium Methylation 450 K data were obtained from 23 of 73 middle age men without clinically evident cardiovascular disease (CVD) who participated in the Aragon Workers Health Study in 2009 (baseline visit) and had available baseline urinary metals and subclinical atherosclerosis measures obtained in 2010–2013 (follow-up visit). The median metal levels were 7.36 μg g-1, 0.33 μg g-1, 0.11 μg g-1 and 0.07 μg g-1, for arsenic (sum of inorganic and methylated species), cadmium, antimony and tungsten, respectively. Urine cadmium and tungsten were associated with femoral and carotid intima-media thickness, respectively (Pearson’s r = 0.27; p = 0.03 in both cases). Among nearest genes to identified differentially methylated regions (DMRs), 46% of metal-DMR genes overlapped with atherosclerosis-DMR genes (p < 0.001). Pathway enrichment analysis of atherosclerosis-DMR genes showed a role in inflammatory, metabolic and transport pathways. In in silico protein-to-protein interaction networks among proteins encoded by 162 and 108 genes attributed to atherosclerosis- and metal-DMRs, respectively, with proteins known to have a role in atherosclerosis pathways, we observed hub proteins in the network associated with both atherosclerosis and metal-DMRs (e.g. SMAD3 and NOP56), and also hub proteins associated with metal-DMRs only but with relevant connections with atherosclerosis effectors (e.g. SSTR5, HDAC4, AP2A2, CXCL12 and SSTR4). Our integrative in silico analysis demonstrates the feasibility of identifying epigenomic regions linked to environmental exposures and potentially involved in relevant pathways for human diseases. While our results support the hypothesis that metal exposures can influence health due to epigenetic changes, larger studies are needed to confirm our pilot results.

Original languageEnglish (US)
Article number20170084
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume373
Issue number1748
DOIs
StatePublished - Jun 5 2018

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middle-aged adults
health care workers
atherosclerosis
Epigenomics
epigenetics
Computer Simulation
Atherosclerosis
Metals
metals
Health
Genes
tungsten
Proteins
Tungsten
proteins
Cadmium
genes
cadmium
antimony
Protein Interaction Maps

Keywords

  • Cohort study
  • DNA methylation
  • Environmental metals
  • Subclinical atherosclerosis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

In silico epigenetics of metal exposure and subclinical atherosclerosis in middle aged men : Pilot results from the aragon workers health study. / Riffo-Campos, Angela L.; Fuentes-Trillo, Azahara; Tang, Wan-Yee; Soriano, Zoraida; De Marco, Griselda; Rentero-Garrido, Pilar; Adam-Felici, Victoria; Lendinez-Tortajada, Veronica; Francesconi, Kevin; Goessler, Walter; Ladd-Acosta, Christine Marie; Leon-Latre, Montse; Casasnovas, Jose A.; Chaves, F. Javier; Navas Acien, Ana; Guallar, Eliseo; Tellez-Plaza, Maria.

In: Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 373, No. 1748, 20170084, 05.06.2018.

Research output: Contribution to journalArticle

Riffo-Campos, AL, Fuentes-Trillo, A, Tang, W-Y, Soriano, Z, De Marco, G, Rentero-Garrido, P, Adam-Felici, V, Lendinez-Tortajada, V, Francesconi, K, Goessler, W, Ladd-Acosta, CM, Leon-Latre, M, Casasnovas, JA, Chaves, FJ, Navas Acien, A, Guallar, E & Tellez-Plaza, M 2018, 'In silico epigenetics of metal exposure and subclinical atherosclerosis in middle aged men: Pilot results from the aragon workers health study', Philosophical Transactions of the Royal Society B: Biological Sciences, vol. 373, no. 1748, 20170084. https://doi.org/10.1098/rstb.2017.0084
Riffo-Campos, Angela L. ; Fuentes-Trillo, Azahara ; Tang, Wan-Yee ; Soriano, Zoraida ; De Marco, Griselda ; Rentero-Garrido, Pilar ; Adam-Felici, Victoria ; Lendinez-Tortajada, Veronica ; Francesconi, Kevin ; Goessler, Walter ; Ladd-Acosta, Christine Marie ; Leon-Latre, Montse ; Casasnovas, Jose A. ; Chaves, F. Javier ; Navas Acien, Ana ; Guallar, Eliseo ; Tellez-Plaza, Maria. / In silico epigenetics of metal exposure and subclinical atherosclerosis in middle aged men : Pilot results from the aragon workers health study. In: Philosophical Transactions of the Royal Society B: Biological Sciences. 2018 ; Vol. 373, No. 1748.
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