Polymorphisms in ABC transporter genes and concentrations of mercury in newborns--evidence from two Mediterranean birth cohorts.
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.


CONCLUSIONS
The ABC transporters appear to play a role in accumulation of MeHg during early development.
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.
Sabrina
S
Llop
Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
Karin
K
Engström
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; School of Nursing, University of Valencia, Valencia, Spain.
Ferran
F
Ballester
Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
Elisa
E
Franforte
Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
Ayman
A
Alhamdow
Unit of Hygiene and Epidemiology, University of Udine, Udine, Italy.
Federica
F
Pisa
Department of Environmental Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.
Janja Snoj
JS
Tratnik
Department of Environmental Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.
Datja
D
Mazej
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.
Mario
M
Murcia
Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; Medicine Department, Jaume I University, Castelló de la Plana, Spain.
Marisa
M
Rebagliato
Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Hospital del Mar Research Institute (IMIM), Barcelona, Spain; Center for Genomic Regulation (CRG), Barcelona, Spain.
Mariona
M
Bustamante
Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain; Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; Hospital del Mar Research Institute (IMIM), Barcelona, Spain; Pompeu Fabra University (UPF), Barcelona, Spain.
Jordi
J
Sunyer
Department of Social and Developmental Paediatrics Institute of Child Health, Athens, Greece.
Alphaikaterini
A
Sofianou-Katsoulis
Department of Social and Developmental Paediatrics Institute of Child Health, Athens, Greece.
Alexia
A
Prasouli
Department of Social and Developmental Paediatrics Institute of Child Health, Athens, Greece.
Eleni
E
Antonopoulou
Department of Social and Developmental Paediatrics Institute of Child Health, Athens, Greece.
Ioanna
I
Antoniadou
Department of Social and Developmental Paediatrics Institute of Child Health, Athens, Greece.
Sheena
S
Nakou
Unit of Hygiene and Epidemiology, University of Udine, Udine, Italy.
Fabio
F
Barbone
Department of Environmental Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.
Milena
M
Horvat
Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Karin
K
Broberg
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D015331:Cohort Studies; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005396:Fish Products; D005787:Gene Frequency; D005838:Genotype; D006115:Greece; D006801:Humans; D007231:Infant, Newborn; D007558:Italy; D018811:Maternal Exposure; D008628:Mercury / Q000097:blood*; D000089762:Multidrug Resistance-Associated Protein 2; D011110:Polymorphism, Genetic; D011247:Pregnancy; D013030:Spain; D011795:Surveys and Questionnaires; D055815:Young Adult
C000715087:ABCC2 protein, human; D018528:ATP-Binding Cassette Transporters; D000089762:Multidrug Resistance-Associated Protein 2; D008628:Mercury