Polymorphisms in ATP-binding cassette transporters associated with maternal methylmercury disposition and infant neurodevelopment in mother-infant pairs in the Seychelles Child Development Study
Polymorphisms in ATP-binding cassette transporters associated with maternal methylmercury disposition and infant neurodevelopment in mother-infant pairs in the Seychelles Child Development Study
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DOI：
10.1016/j.envint.2016.05.027
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发表时间：
2016-09-01
影响因子：
11.8
通讯作者：
Broberg, Karin
中科院分区：
文献类型：
--
作者：
Engstrom, Karin;Love, Tanzy M.;Broberg, Karin
背景：在实验动物模型中，三磷酸腺苷结合盒转运体(ABC)转运体与甲基汞(MeHg)毒性有关。目的：评价母体ABC转运体基因的单核苷酸多态性(SNPs)与1)孕期母体毛发甲基汞浓度及2)儿童神经发育结局的关系。材料和方法：营养队列2(NC2)是2008-2011年在塞舌尔共和国招募的观察性母子队列。孕妇在怀孕期间生长的毛发中的总汞(Hg)被测量为产前甲基汞暴露的生物标志(N=1313)(平均3.9ppm)。婴儿在20个月时完成贝利婴儿发育量表II(BSID-II)的发育评估(N=1331)。结果：ABCC1rs11075290、rs212093和rs215088；ABCC2rs717620；ABCB1rs10276499、rs1202169和rs2032582等7个SNPs与母亲头发汞浓度相关(p<；0.001~0.013)。一个SNP(ABCC1rs11075290)也与神经发育显著相关；母亲携带Rs1 1075290 CC基因(平均头发汞3.6ppm)的孩子的智力发育指数(MDI)和精神运动发育指数(PDI)平均比TT型(平均头发汞4.7ppm)低2分，而CT基因携带者(平均头发汞4.0ppm)的孩子BSID评分中等。甲基汞剂量对发育中儿童和神经发育结果的影响需要进一步调查。(C)2016年提交人。爱思唯尔有限公司出版。
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 rs1 1075290 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. (C) 2016 The Authors. Published by Elsevier Ltd.