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- Engström, Karin, et al.
(författare)
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Polymorphisms in ATP-binding cassette transporters associated with maternal methylmercury disposition and infant neurodevelopment in mother-infant pairs in the Seychelles Child Development Study
- 2016
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 94, s. 224-229
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Tidskriftsartikel (refereegranskat)abstract
- Background: ATP-binding cassette (ABC) transporters have been associated with methylmercury (MeHg) toxicity in experimental animal models. Aims: To evaluate the association of single nucleotide polymorphisms (SNPs) in maternal ABC transporter genes with 1) maternal hair MeHg concentrations during pregnancy and 2) child neurodevelopmental outcomes. Materials and methods: Nutrition Cohort 2 (NC2) is an observational mother-child cohort recruited in the Republic of Seychelles from 2008-2011. Total mercury (Hg) was measured in maternal hair growing during pregnancy as a biomarker for prenatal MeHg exposure (N = 1313) (mean 3.9 ppm). Infants completed developmental assessments by Bayley Scales of Infant Development II (BSID-II) at 20 months of age (N = 1331). Genotyping for fifteen SNPs in ABCC1, ABCC2 and ABCB1 was performed for the mothers. Results: Seven of fifteen ABC SNPs (ABCC1 rs11075290, rs212093, and rs215088; ABCC2 rs717620; ABCB1 rs10276499, rs1202169, and rs2032582) were associated with concentrations of maternal hair Hg (p < 0.001 to 0.013). One SNP (ABCC1 rs11075290) was also significantly associated with neurodevelopment; children born to mothers with rs11075290 CC genotype (mean hair Hg 3.6 ppm) scored on average 2 points lower on the Mental Development Index (MDI) and 3 points lower on the Psychomotor Development Index (PDI) than children born to mothers with TT genotype (mean hair Hg 4.7 ppm) while children with the CT genotype (mean hair Hg 4.0 ppm) had intermediate BSID scores. Discussion: Genetic variation in ABC transporter genes was associated with maternal hair Hg concentrations. The implications for MeHg dose in the developing child and neurodevelopmental outcomes need to be further investigated.
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| 2. |
- Love, Tanzy M, et al.
(författare)
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Contribution of child ABC-transporter genetics to prenatal MeHg exposure and neurodevelopment
- 2022
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Ingår i: NeuroToxicology. - : Elsevier BV. - 1872-9711 .- 0161-813X. ; 91, s. 228-233
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Tidskriftsartikel (refereegranskat)abstract
- 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 29.99µg/L MeHg in cord blood while those homozygous for the C-allele had on average 38.06µg/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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