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Manganese transporter genetics and sex modify the association between environmental manganese exposure and neurobehavioral outcomes in children

2019; Wolters Kluwer; Volume: 3; Issue: Supplement 1 Linguagem: Inglês

10.1097/01.ee9.0000610696.78605.76

2474-7882

Karin Wahlberg, Taj T, Stefano Guazzetti, Marco Peli, Giuseppa Cagna, Donatella Placidi, Robert O. Wright, David S. Smith, Roberto G. Lucchini, Karin Broberg,

Human Health and Disease

TPS 636: Metals and health 2, Johan Friso Foyer, Floor 1, August 28, 2019, 3:00 PM - 4:30 PM There is increasing evidence that environmental manganese (Mn) exposure early in life can have negative effects on children's neurodevelopment including neurobehavioral phenotypes. We have evaluated the influence of sex and polymorphisms in Mn transporter genes SLC30A10 and SLC39A8 on the relationships between environmental Mn exposure and neurobehavioral outcomes in children. Three SNP were genotyped by TaqMan or pyrosequencing in a population of Italian children (aged 11-14 years; n=645) with varying environmental Mn exposure. Mn in surface soil was measured in situ using XRF technology and modeled with geospatial analysis. Linear regression models or generalized additive models (GAM) were used for analyzing associations between soil Mn (Mn exposure) and neurobehavioral problems assessed by the Conners' behavior rating scales (self-, and parent-reported). Gene-environment interactions were evaluated using a genetic score in which genotypes were combined based on their associations with blood Mn, as an indication of Mn regulatory ability. We observed differences in associations between soil Mn and neurobehavior between sexes. Girls showed U-shaped relationships with a positive association between soil Mn and higher (worse) Conners' self-reported scales at the higher soil Mn levels, whereas the parent-reported scales showed positive linear relationships with soil Mn. For boys, we observed a positive linear relationship with soil Mn for one Conner's subtest only (hyperactivity, parent-reported). We also observed interactions between soil Mn and the genetic score on neurobehavior in girls; girls with high Mn genotypes showed more positive associations between Mn in soil and Conners' scores, i.e., increasing problematic behavior with increasing Mn exposure. Our results indicate that that both sex and genetic variation in Mn transporters contribute to differences in sensitivity to Mn exposure from the environment and that girls that are genetically less efficient at regulating Mn, may be a particularly vulnerable group.