Karin Wahlberg1, Tanzy M Love2, Daniela Pineda1, Karin Engström1, Gene E Watson2, Sally W Thurston2, Alison J Yeates3, Maria S Mulhern3, Emeir M McSorley3, J J Strain3, Tristram H Smith1, Philip W Davidson2, Conrad F Shamlaye4, G J Myers2, Matthew D Rand2, Edwin van Wijngaarden2, Karin Broberg5. 1. Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, 22185 Lund, Sweden. 2. University of Rochester Medical Center, School of Medicine and Dentistry, 601 Elmwood Ave, Rochester, NY 14642, USA. 3. Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Cromore Road, Coleraine BT52 1SA, Co. Londonderry, UK. 4. The Child Development Centre, Ministry of Health, Mahé, Seychelles. 5. Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, 22185 Lund, Sweden; Institute of Environmental Medicine, Metals and Health, Box 210, 171 77 Stockholm, Sweden. Electronic address: karin.broberg@ki.se.
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.
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:GCLCrs761142 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 GCLCrs761142 and GCLMrs41303970, 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 GSTP1rs1695 and maternal hair Hg or between any genotypes and maternal blood Hg or cord blood Hg. The maternal GSTP1rs1695 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 GCLCrs761142 TT carriers; and increasing Hg in hair was associated with lower MDI among GSTP1rs1695 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.
Authors: Carolina Johansson; Anna F Castoldi; Natalia Onishchenko; Luigi Manzo; Marie Vahter; Sandra Ceccatelli Journal: Neurotox Res Date: 2007-04 Impact factor: 3.911
Authors: Karin Wahlberg; Manish Arora; Austen Curtin; Paul Curtin; Robert O Wright; Donald R Smith; Roberto G Lucchini; Karin Broberg; Christine Austin Journal: Neurotoxicology Date: 2017-09-13 Impact factor: 4.294
Authors: Edwin van Wijngaarden; Sally W Thurston; Gary J Myers; Donald Harrington; Deborah A Cory-Slechta; J J Strain; Gene E Watson; Grazyna Zareba; Tanzy Love; Juliette Henderson; Conrad F Shamlaye; Philip W Davidson Journal: Neurotoxicol Teratol Date: 2016-10-28 Impact factor: 3.763
Authors: J J Strain; Alison J Yeates; Edwin van Wijngaarden; Sally W Thurston; Maria S Mulhern; Emeir M McSorley; Gene E Watson; Tanzy M Love; Tristram H Smith; Kelley Yost; Donald Harrington; Conrad F Shamlaye; Juliette Henderson; Gary J Myers; Philip W Davidson Journal: Am J Clin Nutr Date: 2015-01-21 Impact factor: 7.045
Authors: P W Davidson; G J Myers; C Cox; C Axtell; C Shamlaye; J Sloane-Reeves; E Cernichiari; L Needham; A Choi; Y Wang; M Berlin; T W Clarkson Journal: JAMA Date: 1998-08-26 Impact factor: 56.272
Authors: Rajendra Prasad Parajuli; Jaclyn M Goodrich; Hwai-Nan Chou; Stephen E Gruninger; Dana C Dolinoy; Alfred Franzblau; Niladri Basu Journal: Environ Res Date: 2015-12-07 Impact factor: 6.498
Authors: Sarah U Morton; Brian J Leyshon; Eleonora Tamilia; Rutvi Vyas; Michaela Sisitsky; Imran Ladha; John B Lasekan; Matthew J Kuchan; P Ellen Grant; Yangming Ou Journal: Front Psychiatry Date: 2022-06-23 Impact factor: 5.435
Authors: Lisa M Prince; M Diana Neely; Emily B Warren; Morgan G Thomas; Madeline R Henley; Kiara K Smith; Michael Aschner; Aaron B Bowman Journal: Food Chem Toxicol Date: 2021-04-05 Impact factor: 5.572
Authors: Matthew D Rand; Daria Vorojeikina; Ashley Peppriell; Jakob Gunderson; Lisa M Prince Journal: Front Genet Date: 2019-08-09 Impact factor: 4.599