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Prenatal methylmercury exposure and genetic predisposition to cognitive deficit at age 8 years.


ABSTRACT: BACKGROUND:Cognitive consequences at school age associated with prenatal methylmercury (MeHg) exposure may need to take into account nutritional and sociodemographic cofactors as well as relevant genetic polymorphisms. METHODS:A subsample (n = 1,311) of the Avon Longitudinal Study of Parents and Children (Bristol, UK) was selected, and mercury (Hg) concentrations were measured in freeze-dried umbilical cord tissue as a measure of MeHg exposure. A total of 1135 children had available data on 247 single-nucleotide polymorphisms (SNPs) within relevant genes, as well as the Wechsler Intelligence Scale for Children Intelligence Quotient (IQ) scores at age 8 years. Multivariate regression models were used to assess the associations between MeHg exposure and IQ and to determine possible gene-environment interactions. RESULTS:Hg concentrations indicated low background exposures (mean = 26 ng/g, standard deviation = 13). Log10-transformed Hg was positively associated with IQ, which attenuated after adjustment for nutritional and sociodemographic cofactors. In stratified analyses, a reverse association was found in higher social class families (for performance IQ, P value for interaction = 0.0013) among whom there was a wider range of MeHg exposure. Among 40 SNPs showing nominally significant main effects, MeHg interactions were detected for rs662 (paraoxonase 1) and rs1042838 (progesterone receptor) (P < 0.05) and for rs3811647 (transferrin) and rs2049046 (brain-derived neurotrophic factor) (P < 0.10). CONCLUSIONS:In this population with a low level of MeHg exposure, there were only equivocal associations between MeHg exposure and adverse neuropsychological outcomes. Heterogeneities in several relevant genes suggest possible genetic predisposition to MeHg neurotoxicity in a substantial proportion of the population. Future studies need to address this possibility.

SUBMITTER: Julvez J 

PROVIDER: S-EPMC6477679 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Prenatal methylmercury exposure and genetic predisposition to cognitive deficit at age 8 years.

Julvez Jordi J   Smith George Davey GD   Golding Jean J   Ring Susan S   Pourcain Beate St BS   Gonzalez Juan Ramon JR   Grandjean Philippe P  

Epidemiology (Cambridge, Mass.) 20130901 5


<h4>Background</h4>Cognitive consequences at school age associated with prenatal methylmercury (MeHg) exposure may need to take into account nutritional and sociodemographic cofactors as well as relevant genetic polymorphisms.<h4>Methods</h4>A subsample (n = 1,311) of the Avon Longitudinal Study of Parents and Children (Bristol, UK) was selected, and mercury (Hg) concentrations were measured in freeze-dried umbilical cord tissue as a measure of MeHg exposure. A total of 1135 children had availab  ...[more]

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