AUTHOR=Gundacker Claudia , Graf-Rohrmeister Klaudia , Gencik Martin , Hengstschläger Markus , Holoman Karol , Rosa Petra , Kroismayr Renate , Offenthaler Ivo , Plichta Veronika , Reischer Theresa , Teufl Isabella , Raffesberg Wolfgang , Scharf Sigrid , Köhler-Vallant Birgit , Delissen Zoja , Weiß Stefan , Uhl Maria 

TITLE=Gene Variants Determine Placental Transfer of Perfluoroalkyl Substances (PFAS), Mercury (Hg) and Lead (Pb), and Birth Outcome: Findings From the UmMuKi Bratislava-Vienna Study

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.664946

DOI=10.3389/fgene.2021.664946

ISSN=1664-8021

ABSTRACT=<p>Prenatal exposure to perfluoroalkyl substances (PFAS), bisphenol A (BPA), lead (Pb), total mercury (THg), and methylmercury (MeHg) can affect fetal development. Factors influencing placental transfer rate of these toxins are poorly investigated. Whether prenatal exposure to pollutants has an effect on birth weight is incompletely understood. We therefore aimed (1) to determine placental transfer rates of PFAS, BPA, Pb, THg, and MeHg, (2) to analyze relationships between fetal exposure and birth outcome and (3) to analyze gene variants as mediators of placental transfer rates and birth outcome. Two hundred healthy pregnant women and their newborns participated in the study. BPA, 16 PFAS, THg, MeHg, and Pb were determined using HPLCMS/MS (BPA, PFAS), HPLC-CV-ICPMS (MeHg), CV-AFS (THg), and GF-AAS (Pb). Questionnaires and medical records were used to survey exposure sources and birth outcome. 20 single nucleotide polymorphisms and two deletion polymorphisms were determined by real-time PCR from both maternal and newborn blood. Genotype-phenotype associations were analyzed by categorical regression and logistic regression analysis. Specific gene variants were associated with altered placental transfer of PFAS (<italic>ALAD</italic> Lys59Asn, <italic>ABCG2</italic> Gln141Lys), THg (<italic>UGT</italic> Tyr85Asp, <italic>GSTT1</italic>del, <italic>ABCC1</italic> rs246221) and Pb (<italic>GSTP1</italic> Ala114Val). A certain combination of three gene polymorphisms (<italic>ABCC1</italic> rs246221, <italic>GCLM</italic> rs4130<italic>3970, HFE</italic> His63Asp) was over-represented in newborns small for gestational age. 36% of Austrian and 75% of Slovakian mothers had levels exceeding the HBM guidance value I (2 μg/L) of the German HBM Commission for PFOA. 13% of newborns and 39% of women had Ery-Pb levels above 24 μg/kg, an approximation for the BMDL<sub>01</sub> of 12 μg/L set by the European Food Safety Authority (EFSA). Our findings point to the need to minimize perinatal exposures to protect fetal health, especially those genetically predisposed to increased transplacental exposure.</p>