Associations between Polymorphisms in Phase II Enzymes and Circulating Sex-Steroid Hormones in White Postmenopausal Women
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Objectives: The purpose of this cross-sectional study was to examine whether single nucleotide polymorphisms (SNPs) in enzymes that metabolize sex steroid hormones were associated with the blood levels of these hormones in postmenopausal women and if the use of menopausal hormone therapy (MHT) could modify this association. Methods: Baseline data were collected from 932 postmenopausal women enrolled in the Minnesota Green Tea Trial. Participants filled out a questionnaire about their demographics, lifestyle factors, and medical and reproductive history. Free, bioavailable, and total serum levels of reproductive hormones were measured through liquid chromatography/tandem mass spectrometry. For genotyping of UGT1A1 (rs10928303), UGT1A4 (rs10929301, rs11673726), UGT1A6 (rs1105879, rs2070959, rs6759892), UGT1A8 (rs10167119), UGT2B7 (rs7439366), and SULT1A1 (rs9282861, rs1968752), mass spectrometry based on multiplex methods and TaqMan assays were performed. Adjusted linear models were fit to assess the associations between SNPs and blood hormones using age, body mass index (BMI), and MHT as covariates. Results: The mean age was 59.8 years, and the mean BMI was 25.1 kg/m2. Past or recent use of MHT was reported by 41.2% of the participants. SNPs in SULT1A1 (rs1968752 and rs9282861) and UGT1A4 (rs11673726) genes were significantly associated with estrone levels, whereas SNPs in UGT1A6 (rs6759892) and UGT1A8 (rs10167119) genes were significantly associated with bioavailable estradiol levels. Conclusions: There was no evidence that MHT use modified the association between SNPs and sex-steroid hormone levels; however, further studies are needed to establish the potential clinical significance of UGT1A4 (rs11673726), UGT1A6 (rs6759892), and UGT1A8 (rs10167119) SNPs and the modulation of hormone levels in postmenopausal women.
Abstract
Objectives: The purpose of this cross-sectional study was to examine whether single nucleotide polymorphisms (SNPs) in enzymes that metabolize sex steroid hormones were associated with the blood levels of these hormones in postmenopausal women and if the use of menopausal hormone therapy (MHT) could modify this association. Methods: Baseline data were collected from 932 postmenopausal women enrolled in the Minnesota Green Tea Trial. Participants filled out a questionnaire about their demographics, lifestyle factors, and medical and reproductive history. Free, bioavailable, and total serum levels of reproductive hormones were measured through liquid chromatography/tandem mass spectrometry. For genotyping of UGT1A1 (rs10928303), UGT1A4 (rs10929301, rs11673726), UGT1A6 (rs1105879, rs2070959, rs6759892), UGT1A8 (rs10167119), UGT2B7 (rs7439366), and SULT1A1 (rs9282861, rs1968752), mass spectrometry based on multiplex methods and TaqMan assays were performed. Adjusted linear models were fit to assess the associations between SNPs and blood hormones using age, body mass index (BMI), and MHT as covariates. Results: The mean age was 59.8 years, and the mean BMI was 25.1 kg/m2. Past or recent use of MHT was reported by 41.2% of the participants. SNPs in SULT1A1 (rs1968752 and rs9282861) and UGT1A4 (rs11673726) genes were significantly associated with estrone levels, whereas SNPs in UGT1A6 (rs6759892) and UGT1A8 (rs10167119) genes were significantly associated with bioavailable estradiol levels. Conclusions: There was no evidence that MHT use modified the association between SNPs and sex-steroid hormone levels; however, further studies are needed to establish the potential clinical significance of UGT1A4 (rs11673726), UGT1A6 (rs6759892), and UGT1A8 (rs10167119) SNPs and the modulation of hormone levels in postmenopausal women.
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