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7154740 
Journal Article 
Abstract 
Genetic polymorphisms of GRIN2A and GRIN2B modify the neurobehavioral effects of low-level lead exposure in children 
Woods, JS; Rooney, J; Woods, NF; Martin, MD 
2017 
Yes 
European Journal of Neurology
ISSN: 1351-5101
EISSN: 1468-1331 
24(Suppl. 2) 
669 
English 
WOS:000405530101376 
Background and aims: Lead (Pb) is neurotoxic and children are highly susceptible to this effect, particularly within the context of continuous low-level Pb exposure. A current major challenge is identification of children who may be uniquely susceptible to Pb toxicity because of genetic predisposition. We examined the hypothesis that polymorphic variants of genes encoding the glutamate receptor, ionotropic, N-methyl-D-aspartate receptor subunits 2A and 2B, GRIN2A and GRIN2B, exacerbate the adverse effects of Pb exposure on these processes in children.

Methods: Participants were subjects who participated as children in the Casa Pia Dental Amalgam Clinical Trial and for whom baseline blood Pb concentrations and annual neurobehavioral test results over the 7 year course of the clinical trial were available. Genotyping was performed for variants of GRIN2A (rs727605 and rs1070503) and GRIN2B (rs7301328 and rs1806201) on biological samples acquired from 330 of the original 507 trial participants. Regression modeling strategies were employed to evaluate the association between allelic status, Pb exposure, and neurobehavioral test outcomes.

Results: Numerous significant adverse interaction effects between variants of GRIN2A, individually and in combination, and Pb exposure were observed among both boys and girls, particularly within the domains of Learning & Memory and Executive Function. In contrast, few interaction effects were observed between variants of GRIN2B and Pb exposure.

Conclusion: These findings suggest potentially distinct roles of GRIN2A and GRIN2B on developmental processes underlying learning and memory as well as other neurological functions in children and demonstrate selective modification of Pb effects on these processes by specific variants of GRIN2A. 
3rd Congress of the European Academy of Neurology 
Amsterdam, Netherlands 
June 2017