Maternal polymorphisms in glutathione-related genes are associated with maternal mercury concentrations and early child neurodevelopment in a population with a fish-rich diet

Karin Wahlberg, Tanzy M Love, Daniela Pineda, Karin Engstrom, Gene E Watson, Sally W Thurston, J J Strain, Tristam H Smith, Philip W Davidson, Conrad F Shamlaye, GJ Myers, Matthew D Rand, Edwin van Wijngaarden, Karin Broberg, Alison J. Yeates, Maria S. Mulhern, Emeir M McSorley

Research output: Contribution to journalArticle

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Abstract

Introduction
Glutathione (GSH) pathways play a key role the metabolism and elimination of the neurotoxicant methylmercury (MeHg). We hypothesized that maternal genetic variation linked to GSH pathways could influence MeHg concentrations in pregnant mothers and children and thereby also affect early life development.

Methods
The GCLM (rs41303970, C/T), GCLC (rs761142, T/G) and GSTP1 (rs1695, A/G) polymorphisms were genotyped in 1449 mothers in a prospective study of the Seychellois population with a diet rich in fish. Genotypes were analyzed in association with maternal hair and blood Hg, fetal blood Hg (cord blood Hg), as well as children's mental (MDI) and motor development (PDI; MDI and PDI assessed by Bayley Scales of Infant Development at 20 months). We also examined whether genotypes modified the association between Hg exposure and developmental outcomes.

Results
GCLC rs761142 TT homozygotes showed statistically higher mean maternal hair Hg (4.12 ppm) than G carriers (AG 3.73 and GG 3.52 ppm) (p = 0.037). For the combination of GCLC rs761142 and GCLM rs41303970, double homozygotes TT + CC showed higher hair Hg (4.40 ppm) than G + T carriers (3.44 ppm; p = 0.018). No associations were observed between GSTP1 rs1695 and maternal hair Hg or between any genotypes and maternal blood Hg or cord blood Hg. The maternal GSTP1 rs1695 rare allele (G) was associated with a lower MDI among children (β = −1.48, p = 0.048). We also observed some interactions: increasing Hg in maternal and cord blood was associated with lower PDI among GCLC rs761142 TT carriers; and increasing Hg in hair was associated with lower MDI among GSTP1 rs1695 GG carriers.

Conclusions
Maternal genetic variation in genes involved in GSH synthesis is statistically associated with Hg concentrations in maternal hair, but not in maternal or fetal blood. We observed interactions that suggest maternal GSH genetics may modify associations between MeHg exposure and neurodevelopmental outcomes.
LanguageEnglish
Pages142-149
Number of pages7
JournalEnvironment International
Volume115
Early online date21 Mar 2018
DOIs
Publication statusPublished - Jun 2018

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hair
polymorphism
blood
diet
gene
fish
genotype
genetic variation
methylmercury
mercury
allele
metabolism

Keywords

  • Methylmercury
  • GCLC
  • GCLM
  • neurodevelopment

Cite this

Wahlberg, Karin ; Love, Tanzy M ; Pineda, Daniela ; Engstrom, Karin ; Watson, Gene E ; Thurston, Sally W ; Strain, J J ; Smith, Tristam H ; Davidson, Philip W ; Shamlaye, Conrad F ; Myers, GJ ; Rand, Matthew D ; van Wijngaarden, Edwin ; Broberg, Karin ; Yeates, Alison J. ; Mulhern, Maria S. ; McSorley, Emeir M. / Maternal polymorphisms in glutathione-related genes are associated with maternal mercury concentrations and early child neurodevelopment in a population with a fish-rich diet. In: Environment International. 2018 ; Vol. 115. pp. 142-149.
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title = "Maternal polymorphisms in glutathione-related genes are associated with maternal mercury concentrations and early child neurodevelopment in a population with a fish-rich diet",
abstract = "IntroductionGlutathione (GSH) pathways play a key role the metabolism and elimination of the neurotoxicant methylmercury (MeHg). We hypothesized that maternal genetic variation linked to GSH pathways could influence MeHg concentrations in pregnant mothers and children and thereby also affect early life development.MethodsThe GCLM (rs41303970, C/T), GCLC (rs761142, T/G) and GSTP1 (rs1695, A/G) polymorphisms were genotyped in 1449 mothers in a prospective study of the Seychellois population with a diet rich in fish. Genotypes were analyzed in association with maternal hair and blood Hg, fetal blood Hg (cord blood Hg), as well as children's mental (MDI) and motor development (PDI; MDI and PDI assessed by Bayley Scales of Infant Development at 20 months). We also examined whether genotypes modified the association between Hg exposure and developmental outcomes.ResultsGCLC rs761142 TT homozygotes showed statistically higher mean maternal hair Hg (4.12 ppm) than G carriers (AG 3.73 and GG 3.52 ppm) (p = 0.037). For the combination of GCLC rs761142 and GCLM rs41303970, double homozygotes TT + CC showed higher hair Hg (4.40 ppm) than G + T carriers (3.44 ppm; p = 0.018). No associations were observed between GSTP1 rs1695 and maternal hair Hg or between any genotypes and maternal blood Hg or cord blood Hg. The maternal GSTP1 rs1695 rare allele (G) was associated with a lower MDI among children (β = −1.48, p = 0.048). We also observed some interactions: increasing Hg in maternal and cord blood was associated with lower PDI among GCLC rs761142 TT carriers; and increasing Hg in hair was associated with lower MDI among GSTP1 rs1695 GG carriers.ConclusionsMaternal genetic variation in genes involved in GSH synthesis is statistically associated with Hg concentrations in maternal hair, but not in maternal or fetal blood. We observed interactions that suggest maternal GSH genetics may modify associations between MeHg exposure and neurodevelopmental outcomes.",
keywords = "Methylmercury, GCLC, GCLM, neurodevelopment",
author = "Karin Wahlberg and Love, {Tanzy M} and Daniela Pineda and Karin Engstrom and Watson, {Gene E} and Thurston, {Sally W} and Strain, {J J} and Smith, {Tristam H} and Davidson, {Philip W} and Shamlaye, {Conrad F} and GJ Myers and Rand, {Matthew D} and {van Wijngaarden}, Edwin and Karin Broberg and Yeates, {Alison J.} and Mulhern, {Maria S.} and McSorley, {Emeir M}",
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language = "English",
volume = "115",
pages = "142--149",
journal = "Environment International",
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Wahlberg, K, Love, TM, Pineda, D, Engstrom, K, Watson, GE, Thurston, SW, Strain, JJ, Smith, TH, Davidson, PW, Shamlaye, CF, Myers, GJ, Rand, MD, van Wijngaarden, E, Broberg, K, Yeates, AJ, Mulhern, MS & McSorley, EM 2018, 'Maternal polymorphisms in glutathione-related genes are associated with maternal mercury concentrations and early child neurodevelopment in a population with a fish-rich diet', Environment International, vol. 115, pp. 142-149. https://doi.org/10.1016/j.envint.2018.03.015

Maternal polymorphisms in glutathione-related genes are associated with maternal mercury concentrations and early child neurodevelopment in a population with a fish-rich diet. / Wahlberg, Karin; Love, Tanzy M; Pineda, Daniela; Engstrom, Karin; Watson, Gene E; Thurston, Sally W; Strain, J J; Smith, Tristam H; Davidson, Philip W; Shamlaye, Conrad F; Myers, GJ; Rand, Matthew D; van Wijngaarden, Edwin; Broberg, Karin; Yeates, Alison J.; Mulhern, Maria S.; McSorley, Emeir M.

In: Environment International, Vol. 115, 06.2018, p. 142-149.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Maternal polymorphisms in glutathione-related genes are associated with maternal mercury concentrations and early child neurodevelopment in a population with a fish-rich diet

AU - Wahlberg, Karin

AU - Love, Tanzy M

AU - Pineda, Daniela

AU - Engstrom, Karin

AU - Watson, Gene E

AU - Thurston, Sally W

AU - Strain, J J

AU - Smith, Tristam H

AU - Davidson, Philip W

AU - Shamlaye, Conrad F

AU - Myers, GJ

AU - Rand, Matthew D

AU - van Wijngaarden, Edwin

AU - Broberg, Karin

AU - Yeates, Alison J.

AU - Mulhern, Maria S.

AU - McSorley, Emeir M

N1 - Compliant in UIR; evidence uploaded to 'Other files'

PY - 2018/6

Y1 - 2018/6

N2 - IntroductionGlutathione (GSH) pathways play a key role the metabolism and elimination of the neurotoxicant methylmercury (MeHg). We hypothesized that maternal genetic variation linked to GSH pathways could influence MeHg concentrations in pregnant mothers and children and thereby also affect early life development.MethodsThe GCLM (rs41303970, C/T), GCLC (rs761142, T/G) and GSTP1 (rs1695, A/G) polymorphisms were genotyped in 1449 mothers in a prospective study of the Seychellois population with a diet rich in fish. Genotypes were analyzed in association with maternal hair and blood Hg, fetal blood Hg (cord blood Hg), as well as children's mental (MDI) and motor development (PDI; MDI and PDI assessed by Bayley Scales of Infant Development at 20 months). We also examined whether genotypes modified the association between Hg exposure and developmental outcomes.ResultsGCLC rs761142 TT homozygotes showed statistically higher mean maternal hair Hg (4.12 ppm) than G carriers (AG 3.73 and GG 3.52 ppm) (p = 0.037). For the combination of GCLC rs761142 and GCLM rs41303970, double homozygotes TT + CC showed higher hair Hg (4.40 ppm) than G + T carriers (3.44 ppm; p = 0.018). No associations were observed between GSTP1 rs1695 and maternal hair Hg or between any genotypes and maternal blood Hg or cord blood Hg. The maternal GSTP1 rs1695 rare allele (G) was associated with a lower MDI among children (β = −1.48, p = 0.048). We also observed some interactions: increasing Hg in maternal and cord blood was associated with lower PDI among GCLC rs761142 TT carriers; and increasing Hg in hair was associated with lower MDI among GSTP1 rs1695 GG carriers.ConclusionsMaternal genetic variation in genes involved in GSH synthesis is statistically associated with Hg concentrations in maternal hair, but not in maternal or fetal blood. We observed interactions that suggest maternal GSH genetics may modify associations between MeHg exposure and neurodevelopmental outcomes.

AB - IntroductionGlutathione (GSH) pathways play a key role the metabolism and elimination of the neurotoxicant methylmercury (MeHg). We hypothesized that maternal genetic variation linked to GSH pathways could influence MeHg concentrations in pregnant mothers and children and thereby also affect early life development.MethodsThe GCLM (rs41303970, C/T), GCLC (rs761142, T/G) and GSTP1 (rs1695, A/G) polymorphisms were genotyped in 1449 mothers in a prospective study of the Seychellois population with a diet rich in fish. Genotypes were analyzed in association with maternal hair and blood Hg, fetal blood Hg (cord blood Hg), as well as children's mental (MDI) and motor development (PDI; MDI and PDI assessed by Bayley Scales of Infant Development at 20 months). We also examined whether genotypes modified the association between Hg exposure and developmental outcomes.ResultsGCLC rs761142 TT homozygotes showed statistically higher mean maternal hair Hg (4.12 ppm) than G carriers (AG 3.73 and GG 3.52 ppm) (p = 0.037). For the combination of GCLC rs761142 and GCLM rs41303970, double homozygotes TT + CC showed higher hair Hg (4.40 ppm) than G + T carriers (3.44 ppm; p = 0.018). No associations were observed between GSTP1 rs1695 and maternal hair Hg or between any genotypes and maternal blood Hg or cord blood Hg. The maternal GSTP1 rs1695 rare allele (G) was associated with a lower MDI among children (β = −1.48, p = 0.048). We also observed some interactions: increasing Hg in maternal and cord blood was associated with lower PDI among GCLC rs761142 TT carriers; and increasing Hg in hair was associated with lower MDI among GSTP1 rs1695 GG carriers.ConclusionsMaternal genetic variation in genes involved in GSH synthesis is statistically associated with Hg concentrations in maternal hair, but not in maternal or fetal blood. We observed interactions that suggest maternal GSH genetics may modify associations between MeHg exposure and neurodevelopmental outcomes.

KW - Methylmercury

KW - GCLC

KW - GCLM

KW - neurodevelopment

U2 - 10.1016/j.envint.2018.03.015

DO - 10.1016/j.envint.2018.03.015

M3 - Article

VL - 115

SP - 142

EP - 149

JO - Environment International

T2 - Environment International

JF - Environment International

SN - 0160-4120

ER -