RESUMO
BACKGROUND: Neurodevelopmental disorders (NDDs) like intellectual disability (ID) are highly heritable, but the environment plays an important role. For example, endocrine disrupting chemicals (EDCs), including bisphenol A (BPA) and its analogues, have been termed neuroendocrine disruptors. This study aimed to evaluate the influence of different genetic polymorphisms (SNPs) on cognitive function in Spanish schoolchildren according to dietary bisphenol exposure. METHODS: A total of 102 children aged 6-12 years old were included. Ten SNPs in genes involved in brain development, synaptic plasticity, and neurotransmission (BDNF, NTRK2, HTR2A, MTHFR, OXTR, SLC6A2, and SNAP25) were genotyped. Then, dietary exposure to bisphenols (BPA plus BPS) was estimated and cognitive functions were assessed using the WISC-V Spanish form. RESULTS: BDNF rs11030101-T and SNAP25 rs363039-A allele carriers scored better on the fluid reasoning domain, except for those inheriting the BDNF rs6265-A allele, who had lower scores. Secondly, relevant SNP-bisphenol interactions existed in verbal comprehension (NTRK2 rs10868235 (p-int = 0.043)), working memory (HTR2A rs7997012 (p-int = 0.002), MTHFR rs1801133 (p-int = 0.026), and OXTR rs53576 (p-int = 0.030)) and fluid reasoning (SLC6A2 rs998424 (p-int = 0.004)). CONCLUSIONS: Our findings provide the first proof that exploring the synergistic or additive effects between genetic variability and bisphenol exposure on cognitive function could lead to a better understanding of the multifactorial and polygenic aetiology of NDDs.
Assuntos
Compostos Benzidrílicos , Fator Neurotrófico Derivado do Encéfalo , Cognição , Disruptores Endócrinos , Fenóis , Polimorfismo de Nucleotídeo Único , Humanos , Criança , Fenóis/efeitos adversos , Compostos Benzidrílicos/efeitos adversos , Feminino , Masculino , Espanha , Cognição/efeitos dos fármacos , Disruptores Endócrinos/efeitos adversos , Fator Neurotrófico Derivado do Encéfalo/genética , Exposição Dietética/efeitos adversos , Receptores de Ocitocina/genética , Proteína 25 Associada a Sinaptossoma/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Receptor 5-HT2A de Serotonina/genética , Receptor trkB/genética , Alelos , Genótipo , Glicoproteínas de MembranaRESUMO
Current evidence highlights the importance of the genetic component in obesity and neurodevelopmental disorders (attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and intellectual disability (ID)), given that these diseases have reported an elevated heritability. Additionally, environmental stressors, such as endocrine disrupting chemicals (EDCs) have been classified as obesogens, neuroendocrine disruptors, and microbiota disrupting chemicals (MDCs). For this reason, the importance of this work lies in examining two possible biological mechanistic pathways linking obesity and neurodevelopmental/behavioural disorders: EDCs - gene and EDCs - microbiota interactions. First, we summarise the shared mechanisms of action of EDCs and the common genetic profile in the bidirectional link between obesity and neurodevelopment. In relation to interaction models, evidence from the reviewed studies reveals significant interactions between pesticides/heavy metals and gene polymorphisms of detoxifying and neurotransmission systems and metal homeostasis on cognitive development, ASD and ADHD symptomatology. Nonetheless, available literature about obesity is quite limited. Importantly, EDCs have been found to induce gut microbiota changes through gut-brain-microbiota axis conferring susceptibility to obesity and neurodevelopmental disorders. In view of the lack of studies assessing the impact of EDCs - gene interactions and EDCs - mediated dysbiosis jointly in obesity and neurodevelopment, we support considering genetics, EDCs exposure, and microbiota as interactive factors rather than individual contributors to the risk for developing obesity and neurodevelopmental disabilities at the same time.