Background: Developmental neurotoxicity due to prenatal methylmercury exposure seems to vary between populations and may be related to genetic predisposition. Aims: To assess IQ at school age in regard to prenatal methylmercury exposure, while taking into regard relevant genetic polymorphisms. Methods: Stored cord tissue from 1311 subjects of the Avon Longitudinal Study of Parents And Children (Bristol, UK) was freeze-dried and analyzed for mercury as measure of prenatal methylmercury exposure. Within this group, 1135 children had available information on 247 single-nucleotide polymorphisms (SNPs) in 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 methylmercury exposure and IQ and to determine possible gene-environment interactions. Results: Mercury concentrations indicated low background exposures (mean (standard deviation) in ng/g: 26 (13)). IQ and log-10 transformed mercury conentrations showed positive associations, which attenuated after adjustment for nutritional and socio-demographic cofactors. Among 40 SNPs showing nominally significant main effects, methylmercury 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). The strongest negative associations between mercury and IQ were seen in the 175 subjects with at least four mutations in these genes. Conclusions: In this population with a fairly low level of methylmercury exposure, only equivocal associations between methylmercury exposure and adverse neuropsychological outcomes were observed. However, heterogeneities in relevant genes suggested possible genetic predisposition to methylmercury neurotoxicity in a substantial proportion of the population.
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