Genetic variation and urine cadmium levels: ABCC1 effects in the Strong Heart Family Study.

Adult Cadmium / urine Chromosomal Proteins, Non-Histone Genetic Linkage Genotype Humans Multidrug Resistance-Associated Proteins / genetics Phosphoric Diester Hydrolases Polymorphism, Single Nucleotide Quantitative Trait Loci
American Indians Association study Cadmium Heritability Quantitative trait locus linkage

Journal

Environmental pollution (Barking, Essex : 1987)
ISSN: 1873-6424
Titre abrégé: Environ Pollut
Pays: England
ID NLM: 8804476

Informations de publication

Date de publication:
01 May 2021
Historique:
received: 25 09 2020
revised: 03 02 2021
accepted: 07 02 2021
pubmed: 1 3 2021
medline: 7 4 2021
entrez: 28 2 2021
Statut: ppublish

Résumé

Genetic effects are suspected to influence cadmium internal dose. Our objective was to assess genetic determinants of urine cadmium in American Indian adults participating in the Strong Heart Family Study (SHFS). Urine cadmium levels and genotyped short tandem repeat (STR) markers were available on 1936 SHFS participants. We investigated heritability, including gene-by-sex and smoking interactions, and STR-based quantitative trait locus (QTL) linkage, using a variance-component decomposition approach, which incorporates the genetic information contained in the pedigrees. We also used available single nucleotide polymorphisms (SNPs) from Illumina's Metabochip and custom panel to assess whether promising QTLs associated regions could be attributed to SNPs annotated to specific genes. Median urine cadmium levels were 0.44 μg/g creatinine. The heritability of urine cadmium concentrations was 28%, with no evidence of gene-by-sex or -smoking interaction. We found strong statistical evidence for a genetic locus at chromosome 16 determining urine cadmium concentrations (Logarithm of odds score [LOD] = 3.8). Among the top 20 associated SNPs in this locus, 17 were annotated to ABCC1 (p-values from 0.0002 to 0.02), and attenuated the maximum linkage peak by a ∼40%. Suggestive QTL signals (LOD>1.9) in chromosomes 2, 6, 11, 14, and 19, showed associated SNPs in the genes NDUFA10, PDE10A, PLEKHA7, BAZ1A and CHAF1A, respectively. Our findings support that urinary cadmium levels are heritable and influenced by a QTL on chromosome 16, which was explained by genetic variation in ABCC1. Studies with extended sets of genome-wide markers are needed to confirm these findings and to identify additional metabolism and toxicity pathways for cadmium.

Identifiants

DOI: 10.1016/j.envpol.2021.116717 PMID: 33640655 PMC: PMC8026674
pubmed: 33640655
pii: S0269-7491(21)00297-9
doi: 10.1016/j.envpol.2021.116717
pmc: PMC8026674
mid: NIHMS1672822
pii:
doi:

Substances chimiques

BAZ1A protein, human 0
Chromosomal Proteins, Non-Histone 0
Multidrug Resistance-Associated Proteins 0
Cadmium 00BH33GNGH
PDE10A protein, human EC 3.1.4.-
Phosphoric Diester Hydrolases EC 3.1.4.-
multidrug resistance-associated protein 1 Y49M64GZ4Q

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

116717

Subventions

Organisme : NHLBI NIH HHS
ID : U01 HL041654
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES025216
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL090863
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES010349
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL109315
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92019D00030
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL109319
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL109284
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL065521
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92019D00027
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL109301
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL109282
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES009089
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES010126
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL041642
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL041652
Pays : United States
Organisme : NHLBI NIH HHS
ID : 75N92019D00029
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL065520
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES021367
Pays : United States

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Auteurs

Maria Grau-Perez (M)

Area of Cardiometabolic and Renal Risk, Institute for Biomedical Research Hospital Clinic of Valencia (INCLIVA), Valencia, Valencia, Spain; Department of Preventive Medicine and Public Health and Microbiology, Universidad Autonoma de Madrid, Madrid, Madrid, Spain; Department of Statistics and Operational Research, University of Valencia, Valencia, Spain. Electronic address: mgrau@incliva.es.

V Saroja Voruganti (VS)

Department of Nutrition and Nutrition Research Institute, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Poojitha Balakrishnan (P)

School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

Karin Haack (K)

Population Health Program, Texas Biomedical Research Institute, San Antonio, TX, USA.

Walter Goessler (W)

Institute of Chemistry - Analytical Chemistry, Karl-Franzens University of Graz, Graz, Austria.

Nora Franceschini (N)

Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Josep Redón (J)

Area of Cardiometabolic and Renal Risk, Institute for Biomedical Research Hospital Clinic of Valencia (INCLIVA), Valencia, Valencia, Spain; Department of Internal Medicine, Hospital Clinic of Valencia, University of Valencia, Valencia, Valencia, Spain.

Shelley A Cole (SA)

Population Health Program, Texas Biomedical Research Institute, San Antonio, TX, USA.

Ana Navas-Acien (A)

Department of Environmental Health Sciences, Columbia University, New York, NY, USA.

Maria Tellez-Plaza (M)

Area of Cardiometabolic and Renal Risk, Institute for Biomedical Research Hospital Clinic of Valencia (INCLIVA), Valencia, Valencia, Spain; Department of Preventive Medicine and Public Health and Microbiology, Universidad Autonoma de Madrid, Madrid, Madrid, Spain; Department of Chronic Diseases Epidemiology, National Center for Epidemiology, Instituto de Salud Carlos III, Madrid, Madrid, Spain; Department of Environmental Health and Engineering, Johns Hopkins University, Baltimore, MD, USA.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Genetic variation and urine cadmium levels:...
questionsmedicales.fr › Produits chimiques inorganiques › Métaux › Métaux lourds › Cadmium › Genetic variation and urine cadmium levels:...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines chromosomiques nonhistones › Genetic variation and urine cadmium levels:...
questionsmedicales.fr › Phénomènes génétiques › Liaison génétique › Genetic variation and urine cadmium levels:...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Genetic variation and urine cadmium levels:...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Genetic variation and urine cadmium levels:...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Pompes ioniques › Transporteurs d'anions › Transporteurs d'anions organiques › Transporteurs d'anions organiques ATP-dépendants › Protéines associées à la multirésistance aux médicaments › Genetic variation and urine cadmium levels:...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Esterases › Phosphodiesterases › Genetic variation and urine cadmium levels:...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Genetic variation and urine cadmium levels:...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Locus génétiques › Locus de caractère quantitatif › Genetic variation and urine cadmium levels:...