背景:像智力障碍(ID)这样的神经发育障碍(NDD)是高度遗传性的,但是环境起着重要的作用。例如,内分泌干扰化学物质(EDCs),包括双酚A(BPA)及其类似物,被称为神经内分泌干扰物。本研究旨在根据膳食双酚暴露评估不同遗传多态性(SNP)对西班牙学童认知功能的影响。
方法:共纳入102名6-12岁儿童。涉及大脑发育的基因中的十个SNP,突触可塑性,和神经传递(BDNF,NTRK2,HTR2A,MTHFR,OXTR,对SLC6A2和SNAP25)进行基因分型。然后,使用WISC-V西班牙语形式估计膳食中双酚(BPA加BPS)的暴露量,并评估认知功能.
结果:BDNFrs11030101-T和SNAP25rs363039-A等位基因携带者在流体推理域得分更好,除了那些遗传BDNFrs6265-A等位基因的人,分数较低的人。其次,相关的SNP-双酚相互作用存在于言语理解中(NTRK2rs10868235(p-int=0.043)),工作记忆(HTR2Ars7997012(p-int=0.002),MTHFRrs1801133(p-int=0.026),和OXTRrs53576(p-int=0.030))和流体推理(SLC6A2rs998424(p-int=0.004))。
结论:我们的研究结果提供了第一个证据,即探索遗传变异性和双酚暴露对认知功能的协同或累加效应可以更好地理解NDD的多因素和多基因病因。
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.