ABC转运蛋白基因多态性与新生儿体内汞浓度——来自两个地中海地区出生队列的证据
Polymorphisms in ABC transporter genes and concentrations of mercury in newborns--evidence from two Mediterranean birth cohorts.
作者信息
Llop Sabrina, Engström Karin, Ballester Ferran, Franforte Elisa, Alhamdow Ayman, Pisa Federica, Tratnik Janja Snoj, Mazej Datja, Murcia Mario, Rebagliato Marisa, Bustamante Mariona, Sunyer Jordi, Sofianou-Katsoulis Alphaikaterini, Prasouli Alexia, Antonopoulou Eleni, Antoniadou Ioanna, Nakou Sheena, Barbone Fabio, Horvat Milena, Broberg Karin
机构信息
Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, FISABIO, Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
出版信息
PLoS One. 2014 May 15;9(5):e97172. doi: 10.1371/journal.pone.0097172. eCollection 2014.
BACKGROUND
The genetic background may influence methylmercury (MeHg) metabolism and neurotoxicity. ATP binding cassette (ABC) transporters actively transport various xenobiotics across biological membranes.
OBJECTIVE
To investigate the role of ABC polymorphisms as modifiers of prenatal exposure to MeHg.
METHODS
The study population consisted of participants (n = 1651) in two birth cohorts, one in Italy and Greece (PHIME) and the other in Spain (INMA). Women were recruited during pregnancy in Italy and Spain, and during the perinatal period in Greece. Total mercury concentrations were measured in cord blood samples by atomic absorption spectrometry. Maternal fish intake during pregnancy was determined from questionnaires. Polymorphisms (n = 5) in the ABC genes ABCA1, ABCB1, ABCC1 and ABCC2 were analysed in both cohorts.
RESULTS
ABCB1 rs2032582, ABCC1 rs11075290, and ABCC2 rs2273697 modified the associations between maternal fish intake and cord blood mercury concentrations. The overall interaction coefficient between rs2032582 and log2-transformed fish intake was negative for carriers of GT (β = -0.29, 95%CI -0.47, -0.12) and TT (β = -0.49, 95%CI -0.71, -0.26) versus GG, meaning that for a doubling in fish intake of the mothers, children with the rs2032582 GG genotype accumulated 35% more mercury than children with TT. For rs11075290, the interaction coefficient was negative for carriers of TC (β = -0.12, 95%CI -0.33, 0.09), and TT (β = -0.28, 95%CI -0.51, -0.06) versus CC. For rs2273697, the interaction coefficient was positive when combining GA+AA (β = 0.16, 95%CI 0.01, 0.32) versus GG.
CONCLUSION
The ABC transporters appear to play a role in accumulation of MeHg during early development.
背景
遗传背景可能会影响甲基汞（MeHg）的代谢和神经毒性。ATP结合盒（ABC）转运蛋白可主动将各种外源性物质转运穿过生物膜。
目的
研究ABC基因多态性作为产前暴露于甲基汞的修饰因子的作用。
方法
研究人群包括两个出生队列中的参与者（n = 1651），一个在意大利和希腊（PHIME），另一个在西班牙（INMA）。在意大利和西班牙，孕妇在孕期被招募；在希腊，孕妇在围产期被招募。通过原子吸收光谱法测量脐血样本中的总汞浓度。通过问卷调查确定孕妇孕期的鱼类摄入量。在两个队列中分析了ABC基因ABCA1、ABCB1、ABCC1和ABCC2中的多态性（n = 5）。
结果
ABCB1 rs2032582、ABCC1 rs11075290和ABCC2 rs2273697改变了孕妇鱼类摄入量与脐血汞浓度之间的关联。rs2032582与log2转换后的鱼类摄入量之间的总体交互系数，对于GT（β = -0.29，95%CI -0.47，-0.12）和TT（β = -0.49，95%CI -0.71，-0.26）携带者相对于GG携带者为负，这意味着母亲鱼类摄入量翻倍时，rs2032582 GG基因型儿童比TT基因型儿童积累的汞多35%。对于rs11075290，TC（β = -0.12，95%CI -0.33，0.09）和TT（β = -0.28，95%CI -0.51，-0.06）携带者相对于CC携带者的交互系数为负。对于rs2273697，GA + AA（β = 0.16，95%CI 0.01，0.32）相对于GG的交互系数为正。
结论
ABC转运蛋白似乎在早期发育过程中甲基汞的积累中起作用。
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