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Contribution of child ABC-transporter genetics to prenatal MeHg exposure and neurodevelopment

Love, Tanzy M ; Wahlberg, Karin LU ; Pineda, Daniela LU ; Watson, Gene E ; Zareba, Grazyna ; Thurston, Sally W ; Davidson, Philip W ; Shamlaye, Conrad F ; Myers, Gary J and Rand, Matthew , et al. (2022) In NeuroToxicology 91. p.228-233
Abstract

BACKGROUND: There is emerging evidence that exposure to prenatal methylmercury (MeHg) from maternal fish consumption during pregnancy can differ between individuals due to genetic variation. In previous studies, we have reported that maternal polymorphisms in ABC-transporter genes were associated with maternal hair MeHg concentrations, and with children's early neurodevelopmental tests. In this study, we add to these findings by evaluating the contribution of genetic variation in children's ABC-transporter genes to prenatal MeHg exposure and early child neurodevelopmental tests.

METHODS: We genotyped six polymorphisms (rs2032582, rs10276499 and rs1202169 in ABCB1; rs11075290 and rs215088 in ABCC1; rs717620 in ABCC2) in DNA from... (More)

BACKGROUND: There is emerging evidence that exposure to prenatal methylmercury (MeHg) from maternal fish consumption during pregnancy can differ between individuals due to genetic variation. In previous studies, we have reported that maternal polymorphisms in ABC-transporter genes were associated with maternal hair MeHg concentrations, and with children's early neurodevelopmental tests. In this study, we add to these findings by evaluating the contribution of genetic variation in children's ABC-transporter genes to prenatal MeHg exposure and early child neurodevelopmental tests.

METHODS: We genotyped six polymorphisms (rs2032582, rs10276499 and rs1202169 in ABCB1; rs11075290 and rs215088 in ABCC1; rs717620 in ABCC2) in DNA from cord blood and maternal blood of the Seychelles Child Development Study Nutrition Cohort 2. We determined prenatal MeHg exposure by measuring total mercury (Hg) in cord blood by atomic fluorescence spectrometry. We assessed neurodevelopment in children at approximately 20 months using the Bayley Scales of Infant Development (BSID-II). We used linear regression models to analyze covariate-adjusted associations of child genotype with cord MeHg and BSID-II outcomes (Mental Developmental and Psychomotor Developmental Indexes). We also evaluated interactions between genotypes, cord MeHg, and neurodevelopmental outcomes. All models were run with and without adjustment for maternal genotype.

RESULTS: Of the six evaluated polymorphisms, only ABCC1 rs11075290 was associated with cord blood MeHg; children homozygous for the T-allele had on average 29.99µg/L MeHg in cord blood while those homozygous for the C-allele had on average 38.06µg/L MeHg in cord blood (p<0.001). No polymorphisms in the children were associated with either subscale of the BSID. However, the association between cord MeHg and the Mental Developmental Index (MDI) of the BSID differed significantly across the three genotypes of ABCB1 rs10276499 (2df F-test, p=0.045). With increasing cord MeHg, the MDI decreased (slope=-0.091, p=0.014) among children homozygous for the rare C-allele.

CONCLUSIONS: These findings support the possibility that child ABC genetics might influence prenatal MeHg exposure.

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type
Contribution to journal
publication status
published
subject
in
NeuroToxicology
volume
91
pages
228 - 233
publisher
Elsevier
external identifiers
  • pmid:35654246
  • scopus:85131402673
ISSN
1872-9711
DOI
10.1016/j.neuro.2022.05.019
language
English
LU publication?
yes
additional info
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
id
52453d71-202a-45a9-a6a8-77c82383608f
date added to LUP
2022-06-07 09:44:35
date last changed
2024-06-25 10:46:09
@article{52453d71-202a-45a9-a6a8-77c82383608f,
  abstract     = {{<p>BACKGROUND: There is emerging evidence that exposure to prenatal methylmercury (MeHg) from maternal fish consumption during pregnancy can differ between individuals due to genetic variation. In previous studies, we have reported that maternal polymorphisms in ABC-transporter genes were associated with maternal hair MeHg concentrations, and with children's early neurodevelopmental tests. In this study, we add to these findings by evaluating the contribution of genetic variation in children's ABC-transporter genes to prenatal MeHg exposure and early child neurodevelopmental tests.</p><p>METHODS: We genotyped six polymorphisms (rs2032582, rs10276499 and rs1202169 in ABCB1; rs11075290 and rs215088 in ABCC1; rs717620 in ABCC2) in DNA from cord blood and maternal blood of the Seychelles Child Development Study Nutrition Cohort 2. We determined prenatal MeHg exposure by measuring total mercury (Hg) in cord blood by atomic fluorescence spectrometry. We assessed neurodevelopment in children at approximately 20 months using the Bayley Scales of Infant Development (BSID-II). We used linear regression models to analyze covariate-adjusted associations of child genotype with cord MeHg and BSID-II outcomes (Mental Developmental and Psychomotor Developmental Indexes). We also evaluated interactions between genotypes, cord MeHg, and neurodevelopmental outcomes. All models were run with and without adjustment for maternal genotype.</p><p>RESULTS: Of the six evaluated polymorphisms, only ABCC1 rs11075290 was associated with cord blood MeHg; children homozygous for the T-allele had on average 29.99µg/L MeHg in cord blood while those homozygous for the C-allele had on average 38.06µg/L MeHg in cord blood (p&lt;0.001). No polymorphisms in the children were associated with either subscale of the BSID. However, the association between cord MeHg and the Mental Developmental Index (MDI) of the BSID differed significantly across the three genotypes of ABCB1 rs10276499 (2df F-test, p=0.045). With increasing cord MeHg, the MDI decreased (slope=-0.091, p=0.014) among children homozygous for the rare C-allele.</p><p>CONCLUSIONS: These findings support the possibility that child ABC genetics might influence prenatal MeHg exposure.</p>}},
  author       = {{Love, Tanzy M and Wahlberg, Karin and Pineda, Daniela and Watson, Gene E and Zareba, Grazyna and Thurston, Sally W and Davidson, Philip W and Shamlaye, Conrad F and Myers, Gary J and Rand, Matthew and van Wijngaarden, Edwin and Broberg, Karin}},
  issn         = {{1872-9711}},
  language     = {{eng}},
  month        = {{05}},
  pages        = {{228--233}},
  publisher    = {{Elsevier}},
  series       = {{NeuroToxicology}},
  title        = {{Contribution of child ABC-transporter genetics to prenatal MeHg exposure and neurodevelopment}},
  url          = {{http://dx.doi.org/10.1016/j.neuro.2022.05.019}},
  doi          = {{10.1016/j.neuro.2022.05.019}},
  volume       = {{91}},
  year         = {{2022}},
}