Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Environ Res. 2022 Oct;213:113651. doi: 10.1016/j.envres.2022.113651. Epub 2022 Jun 8.
The widely used paraben preservatives have been frequently detected in human urine, and shown to disrupt the endocrine system. Recently, several epidemiologic studies have investigated the associations between paraben exposures and hypertension risk, but findings are inconsistent. Genetic susceptibility variation may contribute to the conflicting results. This study aimed to explore the associations of paraben exposures and their interactions with estrogen receptor genes 1 and 2 (ESR1 and ESR2) polymorphisms with hypertension. We conducted a hospital-based case-control study involving 396 hypertension cases and 396 controls in Wuhan, China. The urinary paraben concentrations were determined using a liquid chromatography-quadrupole time of flight mass spectrometer. The genotyping of ESR1 and ESR2 was performed using the Applied Biosystems 3730 XL sequencer. Multivariable logistic regression models were applied to examine the associations between urinary paraben concentrations and hypertension risk. Gene-environment interactions were estimated on both multiplicative and additive scales. The results showed that urinary ethylparaben (EtP), propylparaben (PrP), and ∑parabens (∑PBs) levels were positively associated with the risk of hypertension (P<0.05). Compared with their reference groups, subjects in the highest tertile of EtP, PrP, and ∑PBs had a 4.05-fold (95% CI: 2.56, 6.41), 2.72-fold (95% CI: 1.76, 4.20), and 1.60-fold (95% CI: 1.08, 2.36) increased risk of hypertension, respectively. When stratified by sex, the hypertensive effect of EtP was more pronounced in males (P = 0.012). Furthermore, interaction analysis showed that PrP exposure interacted with ESR1 rs2234693 polymorphism on hypertension risk, with the significance of multiplicative (P = 0.043) and additive (RERI = 1.27, AP = 0.52). Our results suggested that paraben exposure was positively related to hypertension risk, and that ESR1 rs2234693 polymorphism might modify the parabens exposure-related hypertensive effect.
被广泛使用的对羟基苯甲酸酯防腐剂经常在人类尿液中被检测到，并被证明会扰乱内分泌系统。最近，几项流行病学研究调查了对羟基苯甲酸酯暴露与高血压风险之间的关联，但结果不一致。遗传易感性的差异可能导致了相互矛盾的结果。本研究旨在探讨对羟基苯甲酸酯暴露及其与雌激素受体基因 1 和 2（ESR1 和 ESR2）多态性的相互作用与高血压的关系。我们在中国武汉进行了一项基于医院的病例对照研究，共纳入 396 例高血压病例和 396 例对照。使用液相色谱-四极杆飞行时间质谱仪测定尿液中对羟基苯甲酸酯的浓度。使用应用生物系统 3730 XL 测序仪进行 ESR1 和 ESR2 的基因分型。多变量逻辑回归模型用于检验尿液中对羟基苯甲酸酯浓度与高血压风险之间的关联。在乘法和加法尺度上估计了基因-环境相互作用。结果表明，尿液中乙基对羟基苯甲酸酯（EtP）、丙基对羟基苯甲酸酯（PrP）和∑对羟基苯甲酸酯（∑PBs）水平与高血压风险呈正相关（P<0.05）。与参考组相比，EtP、PrP 和 ∑PBs 最高三分位组的高血压风险分别增加了 4.05 倍（95%CI：2.56，6.41）、2.72 倍（95%CI：1.76，4.20）和 1.60 倍（95%CI：1.08，2.36）。按性别分层时，EtP 对男性高血压的影响更为显著（P=0.012）。此外，交互分析表明，PrP 暴露与 ESR1 rs2234693 多态性在高血压风险上存在交互作用，乘法（P=0.043）和加法（RERI=1.27，AP=0.52）均有统计学意义。我们的结果表明，对羟基苯甲酸酯暴露与高血压风险呈正相关，ESR1 rs2234693 多态性可能改变对羟基苯甲酸酯暴露相关的高血压效应。
