Gene-environment interactions in the associations of PFAS exposure with insulin sensitivity and beta-cell function in a Faroese cohort followed from birth to adulthood.
Adult
Female
Humans
Infant, Newborn
Pregnancy
Alkanesulfonic Acids
/ toxicity
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
Diabetes Mellitus, Type 2
/ genetics
Environmental Pollutants
/ toxicity
Fluorocarbons
/ toxicity
Gene-Environment Interaction
Genetic Predisposition to Disease
Insulin Resistance
Solute Carrier Family 12, Member 3
Insulin
Diabetes
Gene-environment interactions
Perfluoroalkyl substances
Journal
Environmental research
ISSN: 1096-0953
Titre abrégé: Environ Res
Pays: Netherlands
ID NLM: 0147621
Informations de publication
Date de publication:
01 06 2023
01 06 2023
Historique:
received:
16
11
2022
revised:
26
02
2023
accepted:
28
02
2023
pmc-release:
01
06
2024
medline:
17
4
2023
pubmed:
4
3
2023
entrez:
3
3
2023
Statut:
ppublish
Résumé
Exposure to perfluoroalkyl substances (PFAS) has been associated with changes in insulin sensitivity and pancreatic beta-cell function in humans. Genetic predisposition to diabetes may modify these associations; however, this hypothesis has not been yet studied. To evaluate genetic heterogeneity as a modifier in the PFAS association with insulin sensitivity and pancreatic beta-cell function, using a targeted gene-environment (GxE) approach. We studied 85 single-nucleotide polymorphisms (SNPs) associated with type 2 diabetes, in 665 Faroese adults born in 1986-1987. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were measured in cord whole blood at birth and in participants' serum from age 28 years. We calculated the Matsuda-insulin sensitivity index (ISI) and the insulinogenic index (IGI) based on a 2 h-oral glucose tolerance test performed at age 28. Effect modification was evaluated in linear regression models adjusted for cross-product terms (PFAS*SNP) and important covariates. Prenatal and adult PFOS exposures were significantly associated with decreased insulin sensitivity and increased beta-cell function. PFOA associations were in the same direction but attenuated compared to PFOS. A total of 58 SNPs were associated with at least one PFAS exposure variable and/or Matsuda-ISI or IGI in the Faroese population and were subsequently tested as modifiers in the PFAS-clinical outcome associations. Eighteen SNPs showed interaction p-values (P Findings from this study suggest that PFAS-associated changes in insulin sensitivity could vary between individuals as a result of genetic predisposition and warrant replication in independent larger populations.
Sections du résumé
BACKGROUND
Exposure to perfluoroalkyl substances (PFAS) has been associated with changes in insulin sensitivity and pancreatic beta-cell function in humans. Genetic predisposition to diabetes may modify these associations; however, this hypothesis has not been yet studied.
OBJECTIVES
To evaluate genetic heterogeneity as a modifier in the PFAS association with insulin sensitivity and pancreatic beta-cell function, using a targeted gene-environment (GxE) approach.
METHODS
We studied 85 single-nucleotide polymorphisms (SNPs) associated with type 2 diabetes, in 665 Faroese adults born in 1986-1987. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were measured in cord whole blood at birth and in participants' serum from age 28 years. We calculated the Matsuda-insulin sensitivity index (ISI) and the insulinogenic index (IGI) based on a 2 h-oral glucose tolerance test performed at age 28. Effect modification was evaluated in linear regression models adjusted for cross-product terms (PFAS*SNP) and important covariates.
RESULTS
Prenatal and adult PFOS exposures were significantly associated with decreased insulin sensitivity and increased beta-cell function. PFOA associations were in the same direction but attenuated compared to PFOS. A total of 58 SNPs were associated with at least one PFAS exposure variable and/or Matsuda-ISI or IGI in the Faroese population and were subsequently tested as modifiers in the PFAS-clinical outcome associations. Eighteen SNPs showed interaction p-values (P
DISCUSSION
Findings from this study suggest that PFAS-associated changes in insulin sensitivity could vary between individuals as a result of genetic predisposition and warrant replication in independent larger populations.
Identifiants
pubmed: 36868448
pii: S0013-9351(23)00392-4
doi: 10.1016/j.envres.2023.115600
pmc: PMC10101920
mid: NIHMS1884031
pii:
doi:
Substances chimiques
Alkanesulfonic Acids
0
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
EC 1.14.11.33
Environmental Pollutants
0
Fluorocarbons
0
FTO protein, human
EC 1.14.11.33
perfluorooctane sulfonic acid
9H2MAI21CL
perfluorooctanoic acid
947VD76D3L
SLC12A3 protein, human
0
Solute Carrier Family 12, Member 3
0
Insulin
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
115600Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES023515
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES027706
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES021477
Pays : United States
Organisme : NIEHS NIH HHS
ID : R21 ES029328
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Damaskini Valvi reports financial support was provided by National Institute of Environmental Health Sciences. Philippe Grandjean reports a relationship with PFAS-exposed communities that includes: consulting or advisory. Damaskini Valvi reports financial support was provided by National Institute of Environmental Health Sciences. Philippe Grandjean reports financial support was provided by National Institute of Environmental Health Sciences. Pal Weihe reports financial support was provided by Faroese Research Council. Philippe Grandjean reports financial support was provided by Danish Environmental Protection Agency. Karine Audouze reports financial support was provided by European Union Horizon program. Philippe Grandjean reports a relationship with PFAS-exposed communities that includes: paid expert testimony.
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