4.4 Article

Contribution of child ABC-transporter genetics to prenatal MeHg exposure and neurodevelopment

期刊

NEUROTOXICOLOGY
卷 91, 期 -, 页码 228-233

出版社

ELSEVIER
DOI: 10.1016/j.neuro.2022.05.019

关键词

ATP-binding cassette transporters; MDR1; MRP1; MRP2; Neurodevelopment; P-Glycoprotein

资金

  1. US National Institute of Health [R01-ES010219, R03-ES027514, R24 ES029466-01A1, P30-ES01247]
  2. Swedish Research Council for Health, Working Life and Welfare (FORTE)
  3. Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS) [2016-00504]
  4. Karolinska Institutet

向作者/读者索取更多资源

This study suggests that genetic variation in ABC transporter genes in children may contribute to prenatal methylmercury exposure and early neurodevelopment. One specific gene, ABCC1 rs11075290, was associated with cord blood MeHg concentrations, while another gene, ABCB1 rs10276499, showed an interaction effect on the relationship between cord MeHg and the Mental Developmental Index of the Bayley Scales of Infant Development.
Background: There is emerging evidence that exposure to prenatal methylmercury (MeHg) from maternal fish consumption during pregnancy can differ between individuals due to genetic variation. In previous studies, we have reported that maternal polymorphisms in ABC-transporter genes were associated with maternal hair MeHg concentrations, and with children's early neurodevelopmental tests. In this study, we add to these findings by evaluating the contribution of genetic variation in children's ABC-transporter genes to prenatal MeHg exposure and early child neurodevelopmental tests. Methods: We genotyped six polymorphisms (rs2032582, rs10276499 and rs1202169 in ABCB1; rs11075290 and rs215088 in ABCC1; rs717620 in ABCC2) in DNA from cord blood and maternal blood of the Seychelles Child Development Study Nutrition Cohort 2. We determined prenatal MeHg exposure by measuring total mercury (Hg) in cord blood by atomic fluorescence spectrometry. We assessed neurodevelopment in children at approximately 20 months using the Bayley Scales of Infant Development (BSID-II). We used linear regression models to analyze covariate-adjusted associations of child genotype with cord MeHg and BSID-II outcomes (Mental Developmental and Psychomotor Developmental Indexes). We also evaluated interactions between genotypes, cord MeHg, and neurodevelopmental outcomes. All models were run with and without adjustment for maternal genotype. Results: Of the six evaluated polymorphisms, only ABCC1 rs11075290 was associated with cord blood MeHg; children homozygous for the T-allele had on average 29.99 mu g/L MeHg in cord blood while those homozygous for the C-allele had on average 38.06 mu g/L MeHg in cord blood (p < 0.001). No polymorphisms in the children were associated with either subscale of the BSID. However, the association between cord MeHg and the Mental Developmental Index (MDI) of the BSID differed significantly across the three genotypes of ABCB1 rs10276499 (2df F-test, p = 0.045). With increasing cord MeHg, the MDI decreased (slope=-0.091, p = 0.014) among children homozygous for the rare C-allele. Conclusions: These findings support the possibility that child ABC genetics might influence prenatal MeHg exposure.

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