Diabetes Genetic Risk Score Modifies Effect of Bisphenol A Exposure on Deterioration in Glucose Metabolism
Diabetes Genetic Risk Score Modifies Effect of Bisphenol A Exposure on Deterioration in Glucose Metabolism
复制标题
糖尿病遗传风险评分改变了双酚 A 暴露对葡萄糖代谢恶化的影响。
DOI：
10.1210/jc.2015-3039
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发表时间：
2016-01-01
影响因子：
5.8
通讯作者：
Ning, Guang
中科院分区：
文献类型：
--
作者：
Bi, Yufang;Wang, Weiqing;Ning, Guang
背景：流行病学研究显示双酚 A (BPA) 暴露与 2 型糖尿病 (T2D) 风险之间关系的结果不一致。目的：本研究旨在前瞻性研究 BPA 与 T2D 风险和血糖特征纵向变化的关联，特别是检查基因和 BPA 暴露之间的相互作用。设计、设置和参与者：2009 年在基线时进行了一项基于社区的研究，包括 2209 名非糖尿病患者中年和老年受试者随访4年。在基线时测量尿液 BPA 水平。基于在东亚人中识别和验证的 34 种 T2D 常见变异，创建了遗传风险评分 (GRS)。 主要结果指标：根据 1999 年世界卫生组织标准定义了 T2D 事件。在基线和随访时测量空腹 (FPG) 和 2 小时负荷后血糖。结果：多变量逻辑回归分析表明，随着加权 T2D-GRS 的增加，BPA 发生 T2D 的风险没有显着相关性（比值比，1.89；95% 置信区间，每 10 点增量为 1.31-2.72）。 FPG 和负荷后 2 小时血浆葡萄糖的 4 年变化也发现了类似的结果。 GRS 改变了 BPA 暴露对 FPG 4 年变化的影响（交互作用 P = 0.01）。每 1 个单位的 Log_BPA 与 GRS 最高四分位数中的 FPG 增加 0.1 mmol/L (P = .007) 相关； GRS 的下三个四分位数没有发现关联。结论：T2D 遗传易感性显着调节 BPA 暴露与 FPG 水平纵向增加的关联。
Context: Epidemiology studies showed inconsistent results regarding the relationship between bisphenol A (BPA) exposure and risk of type 2 diabetes (T2D).Objective: This study sought to prospectively investigate associations of BPA with incident T2D risk and the longitudinal changes in glycemic traits, particularly examining the interaction between gene and BPA exposure on the associations.Design, Setting, and Participants: A community-based study was conducted at baseline in 2009, including 2209 nondiabetic middle-age and elderly subjects followed for 4 y. Urinary BPA levels were measured at baseline. A genetic risk score (GRS) based on 34 T2D common variants that identified and validated in East Asians was created.Main Outcome Measures: Incident T2D was defined according to the 1999 World Health Organization criteria. Fasting (FPG) and 2-h post-loading plasma glucose were measured at baseline and followup.Results: Multivariable logistic regression analysis demonstrated no significant association of risk of incident T2D with BPA while with increase in the weighted T2D-GRS (odds ratio, 1.89; 95% confidence interval, 1.31-2.72 for each 10-point increment). Similar results were found in 4-y changes of FPG and 2-h post-loading plasma glucose. The GRS modified the effect of BPA exposure on 4-y changes in FPG (P for interaction = .01). Each 1 unit of Log_BPA was associated with 0.1 mmol/L increase in FPG (P = .007) in the highest quartile of GRS; no associations were found in the lower three quartiles of GRS.Conclusions: The T2D genetic susceptibility significantly modulated the association of BPA exposure with longitudinal increase in FPG levels.