The correlation between UDP-glucuronosyltransferase polymorphisms and environmental endocrine disruptors levels in polycystic ovary syndrome patients

Background: In recent years, there has been an interest in whether environmental endocrine disruptors (EEDs) may contribute to the endocrine disorders in patients with polycystic ovary syndrome (PCOS). The clearance of EEDs from the human body is regulated by the glucuronidation of UDP-glucuronosyltransferases (UGT). This study aimed to analyze the relationship of UGT1A1, UGT2B7, and UGT2B15 polymorphisms with the metabolism of EEDs in patients with PCOS. Methods: A total of 357 Chinese women (119 PCOS cases and 238 controls) were genotyped for polymorphisms of UGT1A1(G71R), UGT2B7(H268Y), and UGT2B15(D85Y). The plasma concentrations of EEDs were measured by the gas chromatography-mass spectrometry method. The association between UGT polymorphisms and the serum level of EEDs in patients with PCOS was analyzed. Results: The UGT2B7(H268Y) single nucleotide polymorphism was associated with an increased risk of PCOS. The homozygous polymorphism (TT) of UGT2B7(H268Y) showed higher bisphenol A and PAEs concentrations in serum. However, a single nucleotide polymorphism on UGT2B15(D85Y) expression was associated with a decreased risk of PCOS. Subjects homozygous for the T allele of UGT2B15(D85Y) had a significant effect on phthalates in the blood. In addition, our results also showed that the homozygous polymorphism (TT) of UGT2B7(H268Y) and UGT2B15(D85Y) was associated with the capacity of the excretion of androgen in patients with PCOS. Conclusions: Our study reported the novel associations between the UGT polymorphisms and EEDs concentrations in patients with PCOS, supporting the relevance of genetic differences in EEDs metabolism, which might be considered as an etiology of PCOS.