RT info:eu-repo/semantics/article
T1 Gene-environment interaction analysis of redox-related metals and genetic variants with plasma metabolic patterns in a general population from Spain: The Hortega Study
A1 Galvez Fernandez, Marta
A1 Sanchez-Saez, Francisco
A1 Domingo Relloso, Arce
A1 Rodriguez-Hernandez, Zulema
A1 Tarazona, Sonia
A1 Gonzalez-Marrachelli, Vannina
A1 Grau-Perez, Maria
A1 Morales-Tatay, Jose M.
A1 Amigo, Nuria
A1 Garcia-Barrera, Tamara
A1 Gomez-Ariza, Jose L.
A1 Chaves, F. Javier
A1 Garcia-Garcia, Ana Barbara
A1 Melero, Rebeca
A1 Tellez Plaza, Maria
A1 Redon, Josep
A1 Monleon Salvado, Daniel
A1 Martín Escudero, Juan Carlos
K1 Metals, Metabolomics, Oxidative stress, Candidate genes, Gene-environment interaction,
AB Background: Limited studies have evaluated the joint influence of redox-related metals and genetic variation on metabolic pathways. We analyzed the association of 11 metals with metabolic patterns, and the interacting role of candidate genetic variants, in 1145 participants from the Hortega Study, a population-based sample from Spain.Methods: Urine antimony (Sb), arsenic, barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), molybdenum (Mo) and vanadium (V), and plasma copper (Cu), selenium (Se) and zinc (Zn) were measured by ICP-MS and AAS, respectively. We summarized 54 plasma metabolites, measured with targeted NMR, by estimating metabolic principal components (mPC). Redox-related SNPs (N = 291) were measured by oligo-ligation assay.Results: In our study, the association with metabolic principal component (mPC) 1 (reflecting non-essential and essential amino acids, including branched chain, and bacterial co-metabolism versus fatty acids and VLDL subclasses) was positive for Se and Zn, but inverse for Cu, arsenobetaine-corrected arsenic (As) and Sb. The association with mPC2 (reflecting essential amino acids, including aromatic, and bacterial co-metabolism) was inverse for Se, Zn and Cd. The association with mPC3 (reflecting LDL subclasses) was positive for Cu, Se and Zn, but inverse for Co. The association for mPC4 (reflecting HDL subclasses) was positive for Sb, but inverse for plasma Zn. These associations were mainly driven by Cu and Sb for mPC1; Se, Zn and Cd for mPC2; Co, Se and Zn for mPC3; and Zn for mPC4. The most SNP-metal interacting genes were NOX1, GSR, GCLC, AGT and REN. Co and Zn showed the highest number of interactions with genetic variants associated to enriched endocrine, cardiovascular and neurological pathways.Conclusions: Exposures to Co, Cu, Se, Zn, As, Cd and Sb were associated with several metabolic patterns involved in chronic disease. Carriers of redox-related variants may have differential susceptibility to metabolic alterations associated to excessive exposure to metals.
PB Elsevier Science BV
SN 2213-2317
YR 2022
FD 2022
LK https://uvadoc.uva.es/handle/10324/64968
UL https://uvadoc.uva.es/handle/10324/64968
LA eng
NO Redox Biology, junio 2022, vol. 52, 102314 p.1-12
NO Producción Científica
DS UVaDOC
RD 16-jul-2024