Mercury, APOE, and children's neurodevelopment

• Published in: Neurotoxicology (Park Forest South) Vol. 37; pp. 85 - 92
• Main Authors: Ng, Sharon, Lin, Ching-Chun, Hwang, Yaw-Huei, Hsieh, Wu-Shiun, Liao, Hua-Fang, Chen, Pau-Chung
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.07.2013; Elsevier
• Subjects: Adult; APOE; Apolipoprotein E4 - genetics; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; Chi-Square Distribution; Child Development - drug effects; Child, Preschool; Children's neurodevelopment; Cognition - drug effects; Cord blood mercury; Female; Fetal Blood - chemistry; Food Contamination; Gene-Environment Interaction; General aspects; Gene–environmental interaction; Humans; Infant, Newborn; Language Development; Linear Models; Logistic Models; Male; Medical sciences; Mercury Compounds - adverse effects; Mercury Compounds - blood; Mercury Poisoning, Nervous System - etiology; Mercury Poisoning, Nervous System - genetics; Mercury Poisoning, Nervous System - physiopathology; Metals and various inorganic compounds; Motor Skills - drug effects; Multivariate Analysis; Nervous System - drug effects; Nervous System - growth & development; Neuropsychological Tests; Polymorphism, Genetic; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies; Risk Factors; Shellfish; Toxicology; Water Pollutants, Chemical - adverse effects; Water Pollutants, Chemical - blood; Cord blood mercury; MeHg; CDIIT; Children's neurodevelopment; Gene–environmental interaction; ɛ2; ɛ3; ɛ4; APOE; APOE (protein); Hg; Human; Environmental factor; Nervous system; Blood; Heavy metal; Genotype environment interaction; Apolipoprotein E; Gene―environmental interaction; Umbilical cord; Child; Mercury
• ISSN: 0161-813X; 1872-9711; 1872-9711
• DOI: 10.1016/j.neuro.2013.03.012

•Apoe may modify the adverse effect of mercury on children's neurodevelopment.•A gene-environment interaction of Apoe genetic variants and mercury in relation to neurodevelopment has been found.•Apoe epsilon 4 carriers may be more susceptible to the risk of mercury exposure. The benefit of the nutritious elements in fish is insufficient for explaining the controversial finding regarding prenatal mercury (Hg) exposure and neurodevelopment; the varying frequency of susceptible genes among these populations may shed light on these observations. However, limited studies have been reported on the association between genetic susceptibility of prenatal Hg exposure and child development. Apolipoprotein E (APOE, protein; Apoe, gene) is a major protein transporter expressed in the brain. The Apoe epsilon 4 (ɛ4) allele is associated with poor neural repair function and is a risk factor associated with Alzheimer disease. We conducted a prospective cohort study in 2004 and 2005. In this study, 168 subjects were recruited at delivery and followed up at two years of age, and genetic polymorphisms of Apoe were included to assess genetic susceptibility and to determine the relationship between Hg concentrations in cord blood and neurodevelopment. The results showed that adverse effects on neurodevelopment were consistently associated with prenatal Hg exposure in all subtests of Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) among ɛ4 carriers as assessed by both simple linear and multiple linear regression models. After controlling for confounding factors, statistical significance was found in the subtests of cognition tests (β=−8.47, 95% confidence interval (CI)=−16.10 to −0.84), social tests (β=−11.02, 95% CI=−20.85 to −1.19) and the whole test of CDIIT (β=−10.45, 95% CI=−17.36 to −3.54) in a multiple linear regression model. Additionally, the interaction effect between gene polymorphisms of Apoe and Hg levels was significant in the whole test CDIIT and subtests of cognition, language and fine motor tests. In conclusion, Apoe modifies the adverse effects of cord blood Hg on neurodevelopment at the age of two years.