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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 ( IF 10.3 ) Pub Date : 2018-03-21 , DOI: 10.1016/j.envint.2018.03.015 Karin Wahlberg 1 , Tanzy M Love 2 , Daniela Pineda 1 , Karin Engström 1 , Gene E Watson 2 , Sally W Thurston 2 , Alison J Yeates 3 , Maria S Mulhern 3 , Emeir M McSorley 3 , J J Strain 3 , Tristram H Smith 1 , Philip W Davidson 2 , Conrad F Shamlaye 4 , G J Myers 2 , Matthew D Rand 2 , Edwin van Wijngaarden 2 , Karin Broberg 5
Environment International ( IF 10.3 ) Pub Date : 2018-03-21 , DOI: 10.1016/j.envint.2018.03.015 Karin Wahlberg 1 , Tanzy M Love 2 , Daniela Pineda 1 , Karin Engström 1 , Gene E Watson 2 , Sally W Thurston 2 , Alison J Yeates 3 , Maria S Mulhern 3 , Emeir M McSorley 3 , J J Strain 3 , Tristram H Smith 1 , Philip W Davidson 2 , Conrad F Shamlaye 4 , G J Myers 2 , Matthew D Rand 2 , Edwin van Wijngaarden 2 , Karin Broberg 5
Affiliation
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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.
中文翻译：
谷胱甘肽相关基因中的母亲多态性与富含鱼类饮食的人群中的母亲汞浓度和儿童早期神经发育有关。
简介谷胱甘肽（GSH）途径在神经毒性甲基汞（MeHg）的代谢和消除中起关键作用。我们假设与GSH途径相关的母亲遗传变异可能会影响孕妇母亲和儿童的MeHg浓度，从而也影响生命的早期发展。方法在前瞻性研究塞舌尔族人群中，鱼的饮食丰富，对GCLM（rs41303970，C / T），GCLC（rs761142，T / G）和GSTP1（rs1695，A / G）多态性进行基因分型。分析基因型与母亲头发和血液中的Hg，胎儿血液中的Hg（脐带血中的Hg）以及儿童的心理（MDI）和运动发育有关（PDI； MDI和PDI由贝利婴儿发育量表在20个月时评估）。我们还检查了基因型是否改变了汞暴露与发育结局之间的关联。结果GCLC rs761142 TT纯合子在统计学上显示出比G载体（AG 3.73和GG 3.52 ppm）更高的平均母发Hg（4.12 ppm）（p = 0.037）。对于GCLC rs761142和GCLM rs41303970的组合，双纯合子TT + CC显示的头发Hg（4.40 ppm）比G + T载体（3.44 ppm; p = 0.018）高。GSTP1 rs1695与母体头发Hg之间或任何基因型与母体血液Hg或脐带血Hg之间均未发现任何关联。产妇GSTP1 rs1695罕见等位基因（G）与儿童MDI降低有关（β= -1.48，p = 0.048）。我们还观察到一些相互作用：GCLC rs761142 TT携带者中母体和脐带血中Hg的增加与PDI降低有关；在GSTP1 rs1695 GG携带者中，头发中Hg的增加与MDI降低有关。结论涉及GSH合成的基因中的母体遗传变异与母发中Hg浓度在统计学上相关，但与母体或胎儿血液中Hg浓度无关。我们观察到的相互作用表明母体GSH遗传学可能会改变MeHg暴露与神经发育结局之间的关联。
更新日期：2018-03-22
中文翻译：
谷胱甘肽相关基因中的母亲多态性与富含鱼类饮食的人群中的母亲汞浓度和儿童早期神经发育有关。
简介谷胱甘肽（GSH）途径在神经毒性甲基汞（MeHg）的代谢和消除中起关键作用。我们假设与GSH途径相关的母亲遗传变异可能会影响孕妇母亲和儿童的MeHg浓度，从而也影响生命的早期发展。方法在前瞻性研究塞舌尔族人群中，鱼的饮食丰富，对GCLM（rs41303970，C / T），GCLC（rs761142，T / G）和GSTP1（rs1695，A / G）多态性进行基因分型。分析基因型与母亲头发和血液中的Hg，胎儿血液中的Hg（脐带血中的Hg）以及儿童的心理（MDI）和运动发育有关（PDI； MDI和PDI由贝利婴儿发育量表在20个月时评估）。我们还检查了基因型是否改变了汞暴露与发育结局之间的关联。结果GCLC rs761142 TT纯合子在统计学上显示出比G载体（AG 3.73和GG 3.52 ppm）更高的平均母发Hg（4.12 ppm）（p = 0.037）。对于GCLC rs761142和GCLM rs41303970的组合，双纯合子TT + CC显示的头发Hg（4.40 ppm）比G + T载体（3.44 ppm; p = 0.018）高。GSTP1 rs1695与母体头发Hg之间或任何基因型与母体血液Hg或脐带血Hg之间均未发现任何关联。产妇GSTP1 rs1695罕见等位基因（G）与儿童MDI降低有关（β= -1.48，p = 0.048）。我们还观察到一些相互作用：GCLC rs761142 TT携带者中母体和脐带血中Hg的增加与PDI降低有关；在GSTP1 rs1695 GG携带者中，头发中Hg的增加与MDI降低有关。结论涉及GSH合成的基因中的母体遗传变异与母发中Hg浓度在统计学上相关，但与母体或胎儿血液中Hg浓度无关。我们观察到的相互作用表明母体GSH遗传学可能会改变MeHg暴露与神经发育结局之间的关联。
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