Prenatal Methylmercury Exposure and Genetic Predisposition to Cognitive Deficit at Age 8 Years

Abstract

Background: Cognitive consequences at school age associated with prenatal methylmercury exposure may need to take into account nutritional and socio-demographic cofactors as well as relevant genetic polymorphisms. Methods: A sub-sample (n = 1311) of the Avon Longitudinal Study of Parents And Children (Bristol, UK) was selected and mercury concentrations were measured in freeze-dried umbilical cord tissue as a measure of methylmercury 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 methylmercury exposure and IQ and to determine possible gene-environment interactions. Results: Mercury concentrations indicated low background exposures (mean = 26 ng/g, standard deviation = 13). Log-10-transformed mercury was positively associated with IQ, which attenuated after adjustment for nutritional and socio-demographic cofactors. In stratified analyses, a reverse association was found in higher social class families (p-value for interaction = 0.0013, performance IQ), among whom there was a wider range of methylmercury exposure. 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). Conclusions: In this population with a low level of methylmercury exposure, there were only equivocal associations between methylmercury exposure and adverse neuropsychological outcomes. Heterogeneities in several relevant genes suggest possible genetic predisposition to methylmercury neurotoxicity in a substantial proportion of the population. Future studies need to address this possibility.

Neurobehavioural effects of developmental toxicity

“…29 Some common genetic polymorphisms seem to increase the vulnerability of the developing brain to methylmercury toxicity. 30 Functional MRI scans of people exposed prenatally to excess amounts of methylmercury showed abnormally expanded activation of brain regions in response to sensory stimulation and motor tasks (figure 2). 31 Because some adverse effects might be counterbalanced by essential fatty acids from seafood, statistical adjustment for maternal diet during pregnancy results in stronger methylmercury effects.…”

Prenatal mercury exposure and offspring behaviour in childhood and adolescence

“…(e) It remains possible that differences in metabolism, perhaps the result of different genotypes in either the mother or offspring, may have a confounding effect (e.g. Julvez et al, 2013) or make some individuals susceptible even when the population is not.…”

Mercury Exposure and Heart Rate Variability: a Systematic Review

“…Recently, epidemiological studies have explored gene-mercury interactions for human mercury neurotoxicity and identified possible genetic risk modifiers for mercury exposure [56–59]. Possible gene-environment interactions with mercury for heart rate variability outcomes might be explored in future research.…”