Serum Bisphenol A is an independent risk factor of hyperuricemia: A 6-year prospective study

doi:10.1016/j.semarthrit.2018.03.009

Seminars in Arthritis and Rheumatism

Volume 48, Issue 4, February 2019, Pages 644-648

https://doi.org/10.1016/j.semarthrit.2018.03.009 Get rights and content

Abstract

Objective

This study aims to evaluate whether serum Bisphenol A (BPA) is a risk factor for hyperuricemia.

Methods

In this prospective study, a total of 482 participants without hyperuricemia were enrolled at baseline and followed up for 6 years. Clinical characteristics were recorded, and serum levels of uric acid and BPA were measured. Participants were stratified into tertiles according to low, median, and high baseline serum BPA levels. Regression models were used to analyze associations of serum BPA with the change in uric acid and the risk of developing hyperuricemia.

Results

At baseline, serum concentrations of BPA was 0.51 (0.24–2.37) ng/mL. After 6 years of follow-up, the change in serum uric acid concentration from baseline to the 6-year mark was significantly higher in subjects with higher baseline BPA concentration (0.03 ± 0.19, 0.07 ± 0.21, and 0.11 ± 0.25 mg/dL for low, median, and high tertiles, respectively, P = 0.006). When adjusted for potential confounders, such as age, renal function, and history of diabetes and hypertension, multivariable logistic analyses showed that subjects in the median or high baseline BPA tertiles exhibited a twofold higher risk of 6-year hyperuricemia incidence compared to subjects in the low baseline BPA tertile [odds ratio (OR) = 2.28 (95% CI: 1.05–4.95) for the median tertile; 2.42 (1.07–5.48) for the high tertile, P_{for Trend} = 0.043].

Conclusion

In conclusion, serum BPA is an independent risk factor for hyperuricemia.

Introduction

Abnormalities in purine metabolism lead to hyperuricemia [1]. Hyperuricemia is not only a cause of gout but is also independently associated with cardiovascular diseases, chronic kidney diseases, and mortality [2], [3], [4], [5]. In China, the prevalence of hyperuricemia has rapidly increased from 1.4% to 13.3% over the past 3 decades [6], [7], and a similar trend has been seen in the United States [8], [9]. Determining the etiology of hyperuricemia is important for halting the increasing burden of this disease.

The etiology of hyperuricemia depends upon genetics and environment [1], [10], [11], [12]. Genetics alone do not explain the rapid increase in the prevalence of hyperuricemia over the past decades, and modifiable environmental risk factors need to be identified [10]. The National Health and Nutrition Examination Survey (NHANES) has suggested that environmental pollutants such as arsenic and organochlorine are closely associated with the risk of hyperuricemia [11], [12]. Bisphenol A (BPA) is an environmental endocrine disruptor that is typically used in food containers, so human exposure to BPA is widespread [13]. Epidemiologic studies have shown that elevated BPA exposure is correlated with metabolic disorders (i.e., hypertension and type 2 diabetes) as well as cardiorenal dysfunction [14], [15], [16], [17]. Furthermore, our recent study in animals and cells indicated that BPA may promote hyperuricemia via activating xanthine oxidase [18]. Nevertheless, whether BPA is a risk factor for hyperuricemia remains uncertain and needs to be explored in prospective study [10].

We established a prospective, population-based study to investigate the relationship between BPA exposure and serum uric acid concentrations; furthermore, we analyzed whether serum BPA level is an independent risk factor for hyperuricemia.

Section snippets

Study population and sampling approach

This study is a part of the Environment, Inflammation and Metabolic Diseases Study (EIMDS), which is a prospective study that aimed at identifying the environmental and inflammatory risk factors of metabolic disorders such as diabetes, hypertension, chronic kidney diseases, and hyperuricemia [16], [17], [19], [20]. In the current study, the effect of BPA on the risk of hyperuricemia was evaluated.

Hyperuricemia was defined as a blood uric acid concentration greater than 7 mg/dL in men and 6 mg/dL

Characteristics of participants at baseline

The baseline characteristics of participants are shown in Table 1 and Supplementary Table 1. The 288 men and 194 women without hyperuricemia enrolled in the study were 61.6 ± 11.16 years old. Subjects were stratified into those with low, median, and high tertiles of baseline serum BPA level [0.17 (0.12–0.24), 0.51 (0.39–0.81), 3.39 (2.35–4.92) ng/mL, respectively]. Compared to the participants with lower levels of BPA exposure, subjects with higher BPA exposure exhibited higher levels of

Discussion

In this prospective study, we reported that baseline serum BPA levels had a positive correlation with the annual change in serum uric acid concentration and that baseline serum BPA predicted the 6-year risk of developing hyperuricemia. These findings remained the same when potential confounders were included in statistical models. Our findings suggest that BPA is a risk factor for hyperuricemia.

As an environmental endocrine disruptor, BPA has been shown to be involved in hypertension, type 2

Author’s contributions

Jinbo Hu, Chuan Peng, and Qifu Lidesigned the study, oversaw the data collection, and wrote the manuscript. Jiayu Li and Aipin Zhang conducted the data analysis and contributed to the writing of the manuscript. Linqiang Ma, Yi Yang, and Linkun Zhang contributed to the study design, provided statistical expertise. Qingfeng Cheng contributed to the writing of the manuscript. Rufei Gao assisted with the data collection, and contributed to the writing and editing of the manuscript. Yue Wang and

Financial support information

National Key Research & Development Plan, major project of precision medicine research (2017YFC0909600, sub-project: 2017YFC0909602, 2017YFC0909603). National Key Clinical Specialties Construction Program of China to the Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University; and the National Natural Science Foundation of China (81370954 and 81670785) to Qifu Li; and the Fundamental Science & Advanced Technology Research of Chongqing (Major Project,

Acknowledgments

The authors thank Laboratory of Endocrine and the Laboratory of Lipid & Glucose Metabolism, the First Affiliated Hospital of Chongqing Medical University.

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Cited by (15)

Ultra-processed foods: Cross-sectional and longitudinal association with uric acid and hyperuricemia in ELSA-Brasil
2023, Nutrition, Metabolism and Cardiovascular Diseases
Citation Excerpt :
The change in the microbiota has been related to insulin resistance [54] and increased levels of UA in animals [52]. Moreover, serum levels of bisphenol A, a packaging material of industrialized products, were associated to the annual change in UA levels [51] and the risk for the incidence of HU at six years [51]. Among food groups and components of UPFs, nonalcoholic industrialized beverages appear as the first food group that most contributed to UPFs consumption in this work (33.9%–40.5%) (Supplementary Figs. 1 and 2).
Food intake influences uric acid (UA) levels and hyperuricemia (HU), but evidence on the role of ultra-processed foods (UPFs) are scarce. The association between UPFs consumption and (1) HU prevalence and UA levels; (2) HU cumulative incidence; and (3) UA level change over a 4-year period was investigated.
Cross-sectional and longitudinal analyses were performed using baseline (2008–2010, aged 35–74 years) and second visit (2012–2014) data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Participants with glomerular filtration rate <60 mL/min/1.73 m2, bariatric surgery, implausible caloric intake, and using urate-lowering therapy (ULT) at baseline were excluded (all analyses). Participants with HU at baseline were excluded from longitudinal analyses. UPFs consumption was assessed using a food frequency questionnaire (FFQ) and categorized by the NOVA classification system (100 g/day). HU was defined as UA≥6.8 mg/dL. Linear, logistic, and mixed-effect linear regressions investigated the associations between UPFs consumption and UA/HU, adjusted for covariates. The final samples included 13,923 (cross-sectional) and 10,517 (longitudinal) individuals. The prevalence of HU was 18.7%, and the cumulative incidence was 4.9%. Greater UPFs consumption was associated with a greater prevalence of HU (OR:1.025 95%CI: 1.006; 1.044) and higher UA levels (β:0.024 95%CI: 0.016; 0.032). Every additional consumption of 100 g/day of UPFs raised the 4-year cumulative incidence of HU by 5.6% (95%CI: 1.021; 1.092). However, UPFs were not associated with the pace of UA level changes during the study period.
The present study shows that greater UPFs consumption is associated with another deleterious health consequence: higher UA levels and the risk of having HU.
Associations of exposure to perfluoroalkyl substances with serum uric acid change and hyperuricemia among Chinese women: Results from a longitudinal study
2022, Chemosphere
Citation Excerpt :
Furthermore, stronger associations of serum UA with cardiovascular and metabolic diseases have been observed in females than in males (Fang and Alderman, 2000; Grayson et al., 2011; Tani et al., 2020). Levels of serum UA can be affected by both genetic and environmental factors, such as metals (Sun et al., 2017), residential greenness (Dong et al., 2021), and bisphenol A (Hu et al., 2019). Previous epidemiological studies have reported cross-sectional associations of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), the most widely studied PFASs, with elevated serum UA and higher risk of hyperuricemia among occupational (Costa et al., 2009; Rotander et al., 2015; Sakr et al., 2007) and general populations (Arrebola et al., 2019; Gleason et al., 2015; Jain and Ducatman, 2019; Lin et al., 2020; Scinicariello et al., 2020; Shankar et al., 2011).
Cross-sectional studies have reported associations of perfluorooctanoic acid (PFOA) with concurrent serum uric acid (UA) levels. However, the prospective associations of other commonly detected perfluoroalkyl substances (PFASs) with serum UA and hyperuricemia remain unclear.
A total of 654 females from the Dongfeng-Tongji cohort, who were followed up from 2008 to 2018, were included in this study. We measured their baseline plasma concentrations of six PFASs [including perfluorooctane sulfonic acid (PFOS), PFOA, perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDA), and perfluoroheptanoic acid (PFHpA)], as well as their serum UA levels at both baseline and follow-up visits. General linear and logistic regression models were constructed to explore the associations of each PFAS with annual change of serum UA and incident hyperuricemia. Mixture effects of PFASs were further assessed by using the quantile g-computation approach.
Compared to participants with low PFNA exposure (≤50^th), those with high PFNA exposure (>75^th) had significantly increased annual increment of serum UA [β(95%CI) = 2.58 (0.60, 4.55)]. No significant associations of PFOS, PFOA, PFDA, PFHxS, or PFHpA with serum UA change were observed. Besides, females with high PFOA or PFHpA (>75^th) exposure had higher incident risk of hyperuricemia than those with low exposure (<50^th) [OR (95%CI) = 1.94 (1.00, 3.76) and 1.86 (1.03, 3.36), respectively]. No significant associations of PFOS, PFNA, PFDA, and PFHxS with hyperuricemia risk were observed. Quantile g-computation approach didn't find significant effects of PFAS co-exposure on serum UA change or hyperuricemia incidence.
Our findings suggested exposure to PFASs as a risk factor for hyperuricemia and shed light on hyperuricemia prevention for elderly females.
Association between mixed dioxin exposure and hyperuricemia in U.S. adults: A comparison of three statistical models
2022, Chemosphere
Citation Excerpt :
However, these factors cannot completely explain the hyperuricemia epidemic. Recently, more attention was focused on the impact of environmental pollutants on hyperuricemia (Hu et al., 2019; Scinicariello et al., 2020; Sun et al., 2017). Dioxins are chemical environmental pollutants that can be divided into three major groups: dioxin-like polychlorinated biphenyls (DL-PCBs); polychlorinated dibenzo-p-dioxins (PCDDs); and polychlorinated dibenzofurans (PCDFs) (Arisawa, 2018).
Previous studies on the relationship between dioxin exposures and hyperuricemia have usually been based on multi-chemical linear models. However, the complex nonlinear relationship and interaction between mixed dioxin exposures and hyperuricemia have seldom been studied. In this study, we applied three different statistical models to assess the joint effect of 12 dioxins on hyperuricemia.
A total of 7 dioxin-like polychlorinated biphenyls (DL-PCBs), 3 polychlorinated dibenzo-p-dioxins (PCDDs), and 2 polychlorinated dibenzofurans (PCDFs) were measured in the serum of adults by the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2004. We fitted multivariable logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models to estimate the association of individual and mixed dioxin exposures with hyperuricemia.
Among the 1008 individuals included in our analysis, 20.04% had hyperuricemia. In the multivariable logistic regression established for each single dioxin, PCB28, PCB74, PCB105, PCB118, and 1,2,3,4,6,7,8-HPCDD were positively associated with hyperuricemia. With including all dioxins in the multivariable logistic regression model simultaneously, only PCB28 and 1,2,3,4,6,7,8-HPCDD were positively associated with hyperuricemia. In the WQS regression model, the WQS index was significantly associated (OR (95% CI): 2.32 (1.26, 4.28)) with hyperuricemia, and 1,2,3,4,6,7,8-HPCDD (weighted 0.22) had the largest contribution. In BKMR analysis, a significant positive association was found between mixed dioxin exposure and hyperuricemia when all dioxins were at their 60th percentile or above, compared to their 50th percentile. The univariate exposure-response function showed that PCB105 and PCB118 were positively associated with hyperuricemia.
By comparing the three statistical models, we concluded that the whole-body burden of 12 dioxins was significantly positively associated with hyperuricemia. PCB105, PCB118, and 1,2,3,4,6,7,8-HPCDD played the most important roles in hyperuricemia.
Genome-wide gene-bisphenol A, F and triclosan interaction analyses on urinary oxidative stress markers
2022, Science of the Total Environment
Citation Excerpt :
BPA has a structure similar to estradiol and acts as an estrogen to exert endocrine activity via several cell signing pathways (Murata and Kang, 2018). It has been repeatedly reported that BPA has been related to various adverse health or diseases in human such as obesity (M. Hao et al., 2018), hyperuricemia (Hu et al., 2019; L. Ma et al., 2018), cardiovascular disease (Mouneimne et al., 2017), attention deficit disorder (Tsai et al., 2020; Yoo et al., 2020), and even cancers (J. Li et al., 2020; Z. Wang et al., 2017). In addition, BPF and TCS have also been shown to have different levels of endocrine activity, which are related to many metabolism-related diseases (Chen et al., 2016; Weatherly and Gosse, 2017).
Bisphenols and triclosan (TCS) are common endocrine disrupters (EDCs) that may induce oxidative stress. However, there is limited information as to whether these EDCs interact with genetic variants to modify the levels of oxidative stress on a genome-wide scale.
We first performed a genome-wide scan among a Chinese population and also measured three urinary EDCs, including bisphenol A (BPA), bisphenol F (BPF) and TCS, and three urinary oxidative stress markers [4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), 8-iso-prostaglandin-F_2α (8-isoPGF_2α) and 8-hydroxy-deoxyguanosine (8-OHdG)]. Subsequently, we examined interactions between three urinary EDCs and nearly 4.6 million genetic variants for three urinary oxidative stress markers by the general linear model.
Urinary BPA, BPF and TCS were positively associated with HNE-MA, 8-isoPGF_2α and 8-OHdG. Significant rs6855040 (4p15.32/between SNORA75B and QDPR)-BPA, rs1112943 (4q35.1/SNX25)-TCS interactions were associated with the 8-isoPGF_2α levels (all P < 5 × 10⁻⁸). In addition, rs4656116 (1p22.3/CACL1), rs16958760 (17p11.2/between USP43 and DHRS7C) and rs11651078 (17p11.2/LOC339260) showed significant gene-TCS interactions with 8-OHdG (all P < 5 × 10⁻⁸). The gene-level analysis found significant interaction between SNX25 and TCS for 8-isoPGF_2α levels (P < 2.12 × 10⁻⁶).
Our results identify several gene-EDCs interactions for oxidative stress, highlighting that EDCs may modify the effect of genetic variants on oxidative stress.
Association between consumption of ultra-processed foods and hyperuricemia: TCLSIH prospective cohort study
2021, Nutrition, Metabolism and Cardiovascular Diseases
Citation Excerpt :
Finally, UPF contain authorized but controversial food additives such as sodium benzoate and sodium nitrite [44]. Animal models have suggested these additives can raise serum uric acid levels [45,46]. Of note, Table 1 demonstrates that participants at baseline with higher UPF consumption had lower prevalence of obesity, hypertension, dyslipidemia and diabetes.
Emerging evidence suggests that consumption of ultra-processed foods (UPF) plays a role in the development of chronic diseases, but evidence of their influence on hyperuricemia is limited. We therefore designed a cohort study to examine whether UPF consumption increase the risk of hyperuricemia in adults.
This was a prospective study (n = 18,444) performed in Tianjin, China from 2013 to 2019. Participants that were aged 18 years and over and with no history of hyperuricemia, were followed up for 1–6 years (median follow-up duration = 4.2 years). UPF consumption was assessed by a validated semi-quantitative food frequency questionnaire. Hyperuricemia was defined as serum uric acid levels ≥7.0 mg/dL in males and ≥ 6 mg/dL in females. Multivariable Cox proportional hazards regression models were used to assess the association between UPF consumption and the risk of hyperuricemia. Restricted cubic spline regression was used to estimate the dose–response association between UPF consumption and risk of hyperuricemia. During follow-up period, the incidence of hyperuricemia was 20.3% in general population (27.7% in males and 13.2% in females). In the final multivariate models, the hazard ratios (95% confidence interval) for hyperuricemia across energy adjusted UPF consumption quartiles were 1.00 (reference), 1.04 (0.94, 1.14), 1.11 (1.01, 1.23), 1.16 (1.05, 1.28) (p for trend = 0.02) in general population.
This population-based prospective cohort study suggests that increased consumption of UPF is independently associated the risk of hyperuricemia.
Relationship between the environmental endocrine disruptor bisphenol a and dyslipidemia: A five-year prospective study
2020, Endocrine Practice
Objective: To investigate whether serum bisphenol A (BPA) concentration is related to the occurrence of dyslipidemia.
Methods: A total of 574 adults were enrolled at baseline and followed up for 5 years. Concentrations of serum BPA, triglycerides (TGs), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured. Dyslipidemia was defined as the existence of one or more of the following conditions: high-LDL-cholesterolemia (LDL ≥140 mg/dL), hypertriglyceridemia (TGs ≥150 mg/dL), or low-HDL-cholesterolemia (HDL <40 mg/dL). Participants were stratified into tertiles according to low, median, and high baseline serum BPA levels. Multivariable linear and logistic regression models were used. Data from baseline and follow-up were used for cross-sectional and longitudinal analyses, respectively.
Results: In the cross-sectional analysis, compared to subjects in the low BPA tertile, those in the high BPA tertile showed a higher level of LDL cholesterol (108.1 ± 24.4 mg/dL versus 119.5 ± 26.9 mg/dL; P<.05) and a lower level of HDL cholesterol (46.2 ± 11.7 mg/dL versus 39.5 ± 7.5 mg/dL; P<.05). In multivariable linear regression models, Z-transformed BPA was positively associated with LDL cholesterol (β= 0.13, P = .002) and negatively associated with HDL cholesterol (β= -0.28; P<.001). After cross-sectionally adjusting for confounders, subjects in higher BPA exposure was associated with a higher prevalence of low-HDL-cholesterolemia. Longitudinally, in subjects without low-HDL-cholesterolemia at baseline, each SD increment in baseline BPA was associated with a higher incidence of low-HDL-cholesterolemia after adjustment for confounders (odds ratio [95% confidence interval; CI] 2.76, 95% CI 1.21, 6.29).
Conclusion: Cross-sectionally, higher BPA exposure is associated with a higher prevalence of low-HDL-cholesterolemia. Longitudinally, baseline BPA is an independent predictor of the 5-year incidence of low-HDL-cholesterolemia.
Abbreviations: BMI = body mass index; BPA = bisphenol A; CI = confidence interval; CVD = cardiovascular disease; EIMDS = environment, inflammation and metabolic diseases study; HDL = high density lipoprotein; LDL = low density lipoprotein; OR = odds ratio; PPAR = peroxisome proliferator-activated receptor; SBP = systolic blood pressure; TG = triglyceride; Z-BPA = Z-transformed bisphenol A

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^¹: Co-first authors: Jinbo Hu, Chuan Peng, and Jiayu Li.

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Serum Bisphenol A is an independent risk factor of hyperuricemia: A 6-year prospective study

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Study population and sampling approach

Characteristics of participants at baseline

Discussion

Author’s contributions

Financial support information

Acknowledgments

Metabolism

Metabolism

Atherosclerosis

Environ Int

Metabolism

J Biol Chem

J Mol Cell Cardiol

Food Chem Toxicol

The molecular physiology of uric acid homeostasis

Annu Rev Physiol

Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971–1992. National Health and Nutrition Examination Survey

J Am Med Assoc

Serum uric acid and risk of cardiovascular mortality: a prospective long-term study of 83,683 Austrian men

Clin Chem

The epidemiology study of hyperuricemia and gout in a community population of Huangpu District in Shanghai

Chin Med J (Engl)

Prevalence of hyperuricemia and gout in Mainland China from 2000 to 2014: a systematic review and meta-analysis

Biomed Res Int

Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008

Arthritis Rheum

Increasing prevalence of gout and hyperuricemia over 10 years among older adults in a managed care population

J Rheumatol