Jia Feng, Chang Yu, Li Yuguang, Li Fangqi, Chen Xinqiao, Liu Xiangliang, Li Wei, Cui Jiuwei
The First Hospital of Jilin University, No.1 Xinmin Street, Changchun, 130012, China.
BMC Public Health. 2025 Jan 20;25(1):231. doi: 10.1186/s12889-025-21417-z.
Phthalate exposure has been hypothesized to influence cholesterol metabolism and gallstone pathogenesis, but previous studies are limited. We aimed to examine the associations between urinary phthalate metabolites and prevalence of gallstone disease in a nationally representative sample.
We analyzed data on 1,696 adults aged ≥ 30 years from the National Health and Nutrition Examination Survey (NHANES) 2017-2018. Gallstone disease was defined based on self-reported physician-diagnosis. Exposure was measured by urinary concentrations of 10 phthalate metabolites. Multivariable logistic regression model was to assess individual exposure-effect associations. Weighted quantile sum (WQS) regression, Quantile g-computation (Qgcomp) analysis and Bayesian kernel machine regression (BKMR) assessed metabolite mixtures in relation to gallstones.
In the multivariable logistic regression model, compared to the lowest quartile (Q1) of urinary mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), the highest quartile (Q4) was associated with an 82% increased risk of gallstone formation (OR: 1.82, 95% CI: 1.17, 2.85). Similarly, for mono(3-carboxypropyl) phthalate (MCPP), the risk increased by 78% in the Q4 group compared to Q1 (OR: 1.78, 95% CI: 1.02, 3.14). The WQS index exhibited a significant positive association with gallstone prevalence (OR: 1.37, 95%CI: 1.02, 1.84). In the Qgcomp model, four urinary phthalate metabolites, including MECPP, MCPP, mono benzyl phthalate (MBzP) and mono-carboxynonyl phthalate (MCNP), were positively associated with an increased risk of gallstones. BKMR identified exposure-response trends for MECPP, MCPP, and MBzP.
Higher urinary phthalate metabolite concentrations were associated with increased gallstone risk. These novel findings suggest phthalate exposure may contribute to lithogenic pathogenesis. Future prospective and mechanistic research is warranted.
邻苯二甲酸盐暴露被认为会影响胆固醇代谢和胆结石发病机制，但以往研究有限。我们旨在在一个具有全国代表性的样本中研究尿邻苯二甲酸酯代谢物与胆结石疾病患病率之间的关联。
我们分析了2017 - 2018年美国国家健康与营养检查调查（NHANES）中1696名年龄≥30岁成年人的数据。胆结石疾病根据自我报告的医生诊断来定义。通过10种邻苯二甲酸酯代谢物的尿浓度来衡量暴露情况。多变量逻辑回归模型用于评估个体暴露 - 效应关联。加权分位数和（WQS）回归、分位数g计算（Qgcomp）分析和贝叶斯核机器回归（BKMR）评估了与胆结石相关的代谢物混合物。
在多变量逻辑回归模型中，与尿单（2 - 乙基 - 5 - 羧基戊基）邻苯二甲酸酯（MECPP）的最低四分位数（Q1）相比，最高四分位数（Q4）与胆结石形成风险增加82%相关（比值比：1.82，95%置信区间：1.17，2.85）。同样，对于单（3 - 羧基丙基）邻苯二甲酸酯（MCPP），与Q1相比，Q4组风险增加78%（比值比：1.78，95%置信区间：1.02，3.14）。WQS指数与胆结石患病率呈显著正相关（比值比：1.37，95%置信区间：1.02，1.84）。在Qgcomp模型中，四种尿邻苯二甲酸酯代谢物，包括MECPP、MCPP、单苄基邻苯二甲酸酯（MBzP）和单羧基壬基邻苯二甲酸酯（MCNP），与胆结石风险增加呈正相关。BKMR确定了MECPP、MCPP和MBzP的暴露 - 反应趋势。
尿邻苯二甲酸酯代谢物浓度较高与胆结石风险增加相关。这些新发现表明邻苯二甲酸盐暴露可能促成结石形成发病机制。未来有必要进行前瞻性和机制性研究。
