Paraben exposures and their interactions with ESR1/2 genetic polymorphisms on hypertension

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_trend<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_interaction = 0.012). Furthermore, interaction analysis showed that PrP exposure interacted with ESR1 rs2234693 polymorphism on hypertension risk, with the significance of multiplicative (P_interaction = 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.