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根据双酚类物质和对羟基苯甲酸酯类物质的饮食暴露情况,探讨体重指数遗传多态性的影响。

Effects of genetic polymorphisms in body mass index according to dietary exposure to bisphenols and parabens.

机构信息

Department of Nutrition and Food Science, University of Granada, Cartuja Campus, 18071, Granada, Spain; GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, PTS Granada, Granada, Spain.

Department of Nutrition and Food Science, University of Granada, Cartuja Campus, 18071, Granada, Spain.

出版信息

Chemosphere. 2022 Apr;293:133421. doi: 10.1016/j.chemosphere.2021.133421. Epub 2021 Dec 24.

Abstract

A growing body of evidence supports that more than 900 single nucleotide polymorphisms (SNPs) and exposure to endocrine disrupting chemicals, such as bisphenols and parabens, are important contributors to the development of obesity. The aim of this study was to evaluate the way in which fat mass and obesity-associated gene (FTO) rs9939609 and leptin receptor (LEPR) rs9436303 variants contribute to variability in body mass index (BMI) according to estimated dietary exposure of bisphenols and parabens. This cross-sectional study included 101 Spanish participants (16-24 years). SNP genotyping assays were performed through quantitative PCRs (qPCRs) using Taqman® probes. Dietary exposure to bisphenols and parabens was calculated from food frequency questionnaire and chemical determination in food samples by ultra-high performance liquid chromatography-tandem mass spectrometry system. Linear regression models were conducted to address the association of genetic variants and BMI according to levels of bisphenols/parabens exposure. Risk G allele of LEPR rs9436303 was significantly positively associated with BMI (exp (β) = 1.20, 95% CI: 1.04-1.38, p = 0.011). In participants highly exposed to bisphenols, the LEPR rs9436303 G allele was related to a significant increased BMI (exp (β) = 1.27, 95% CI: 1.03-1.57, p = 0.024). A more relevant trend was observed with high exposure to parabens (exp (β) = 1.33, 95% CI: 1.08-1.63, p = 0.009). We provide the first evidence that interaction between LEPR polymorphism and dietary intake of bisphenols and parabens may be responsible for an increased BMI, suggesting a potential effect in obesity. Moreover, we proposed LEPR rs9436303 as a genetic marker of susceptibility to excess weight induced by exposure.

摘要

越来越多的证据表明,超过 900 个单核苷酸多态性(SNP)和暴露于内分泌干扰化学物质,如双酚和对羟基苯甲酸酯,是肥胖发展的重要因素。本研究旨在评估脂肪量和肥胖相关基因(FTO)rs9939609 和瘦素受体(LEPR)rs9436303 变体在多大程度上根据双酚和对羟基苯甲酸酯的估计膳食暴露情况,导致体重指数(BMI)的变化。这项横断面研究包括 101 名西班牙参与者(16-24 岁)。SNP 基因分型检测通过定量 PCR(qPCR)使用 Taqman®探针进行。通过食物频率问卷和食品样本中化学物质的超高效液相色谱-串联质谱系统测定,计算双酚和对羟基苯甲酸酯的膳食暴露量。线性回归模型用于根据双酚/对羟基苯甲酸酯暴露水平研究遗传变异与 BMI 的关联。LEPR rs9436303 的风险 G 等位基因与 BMI 呈显著正相关(β=1.20,95%置信区间:1.04-1.38,p=0.011)。在高度暴露于双酚的参与者中,LEPR rs9436303 G 等位基因与 BMI 的显著增加有关(β=1.27,95%置信区间:1.03-1.57,p=0.024)。在高度暴露于对羟基苯甲酸酯的情况下,观察到更相关的趋势(β=1.33,95%置信区间:1.08-1.63,p=0.009)。我们提供了第一个证据表明,LEPR 多态性与双酚和对羟基苯甲酸酯的饮食摄入之间的相互作用可能导致 BMI 增加,表明其在肥胖方面具有潜在作用。此外,我们提出 LEPR rs9436303 作为暴露诱导超重的易感性遗传标志物。

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