Urinary phthalate metabolites associated with increased prevalence of gallstone disease in U.S. adults: data from the NHANES study

Abstract Background 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...

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Main Authors: Feng Jia, Yu Chang, Yuguang Li, Fangqi Li, Xinqiao Chen, Xiangliang Liu, Wei Li, Jiuwei Cui
Format: Article
Language:English
Published: BMC 2025-01-01
Series:BMC Public Health
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Online Access:https://doi.org/10.1186/s12889-025-21417-z
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author Feng Jia
Yu Chang
Yuguang Li
Fangqi Li
Xinqiao Chen
Xiangliang Liu
Wei Li
Jiuwei Cui
author_facet Feng Jia
Yu Chang
Yuguang Li
Fangqi Li
Xinqiao Chen
Xiangliang Liu
Wei Li
Jiuwei Cui
author_sort Feng Jia
collection DOAJ
description Abstract Background 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. Methods 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. Results 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. Conclusion 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.
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spelling doaj-art-a54369d312bc44218e04d3d4854e88982025-01-26T12:55:41ZengBMCBMC Public Health1471-24582025-01-0125111410.1186/s12889-025-21417-zUrinary phthalate metabolites associated with increased prevalence of gallstone disease in U.S. adults: data from the NHANES studyFeng Jia0Yu Chang1Yuguang Li2Fangqi Li3Xinqiao Chen4Xiangliang Liu5Wei Li6Jiuwei Cui7The First Hospital of Jilin UniversityThe First Hospital of Jilin UniversityThe First Hospital of Jilin UniversityThe First Hospital of Jilin UniversityThe First Hospital of Jilin UniversityThe First Hospital of Jilin UniversityThe First Hospital of Jilin UniversityThe First Hospital of Jilin UniversityAbstract Background 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. Methods 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. Results 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. Conclusion 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.https://doi.org/10.1186/s12889-025-21417-zPhthalate metabolitesGallstonesEndocrine disrupting chemicalsWeighted quantile sum regressionBayesian kernel machine regression
spellingShingle Feng Jia
Yu Chang
Yuguang Li
Fangqi Li
Xinqiao Chen
Xiangliang Liu
Wei Li
Jiuwei Cui
Urinary phthalate metabolites associated with increased prevalence of gallstone disease in U.S. adults: data from the NHANES study
BMC Public Health
Phthalate metabolites
Gallstones
Endocrine disrupting chemicals
Weighted quantile sum regression
Bayesian kernel machine regression
title Urinary phthalate metabolites associated with increased prevalence of gallstone disease in U.S. adults: data from the NHANES study
title_full Urinary phthalate metabolites associated with increased prevalence of gallstone disease in U.S. adults: data from the NHANES study
title_fullStr Urinary phthalate metabolites associated with increased prevalence of gallstone disease in U.S. adults: data from the NHANES study
title_full_unstemmed Urinary phthalate metabolites associated with increased prevalence of gallstone disease in U.S. adults: data from the NHANES study
title_short Urinary phthalate metabolites associated with increased prevalence of gallstone disease in U.S. adults: data from the NHANES study
title_sort urinary phthalate metabolites associated with increased prevalence of gallstone disease in u s adults data from the nhanes study
topic Phthalate metabolites
Gallstones
Endocrine disrupting chemicals
Weighted quantile sum regression
Bayesian kernel machine regression
url https://doi.org/10.1186/s12889-025-21417-z
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