Evaluation of UGT1A1 and SULT1A1 polymorphisms with lipid levels in women with different hormonal status

Abstract

Background. Estrogens influence many physiological processes including cardiovascular health. Polymorphisms in phase I and II estrogen metabolism enzymes are associated with lipid levels in women.

Methods. A cross-sectional study was carried out with 269 postmenopausal women, 116 who received oral hormonal therapy (HT) (39–75 years) with estrogens or estrogens plus progestagen, 153 that did not receive any HT (38–85 years), and 155 premenopausal women (18–52 years). Polymorphisms in UGT1A1 (rs5839491) and SULT1A1 (rs1042028) were analysed by PCR-based methods. Adjusted lipid levels means were compared among genotypes by one-way analysis of variance, with corrections for multiple testing.

Results. The UGT1A1*28 polymorphism was associated with total cholesterol (T-chol) (p = 0.030; corrected p = 0.060) and low-density lipoprotein cholesterol (LDL-C) levels (p = 0.011, corrected p = 0.022) in premenopausal women. The premenopausal and postmenopausal women, both carriers of SULT1A1*2/*2, had lower levels of T-chol and LDL-C means than carriers of the SULT1A1*1/*1 (p = 0.004, corrected p = 0.008 and 0.009, corrected p = 0.018, respectively).

Conclusion. The data showed the presence of an association between the UGT1A1*28/*28 and SULT1A1*2/*2 and T-chol and LDL-C levels in women with different hormonal status. No previous studies investigated the association of the polymorphisms examined in this study with lipoprotein levels in women separately by hormonal status.

Keywords:

• UDP-glucuronosyltransferase 1A1
• sulfotransferase 1A1
• hormonal therapy
• cardiovascular disease
• lipid levels
• pharmacogenetics

Acknowledgements

Thanks are due to Ana Lúcia S. Antunes and Maria Perpétua de O. Pinto from the Clinical Analysis Laboratory of the Pharmacy College. Financial support was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil).