Document Detail


Associations between polymorphisms in glucuronidation and sulfation enzymes and sex steroid concentrations in premenopausal women in the United States.
MedLine Citation:
PMID:  21193038     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glucuronidation, catalyzed by UDP-glucuronosyltransferases (UGT) and sulfation, catalyzed by sulfotransferases (SULT), are pathways through which sex steroids are metabolized to less active compounds. These enzymes are highly polymorphic and genetic variants frequently result in higher or lower activity. The phenotypic effects of these polymorphisms on circulating sex steroids in premenopausal women have not yet been investigated. One hundred and seventy women aged 40-45 years had a blood sample drawn during the follicular phase of the menstrual cycle for sex steroid measures and to obtain genomic DNA. Urine was collected for 2-hydroxy (OH) estrone (E(1)) and 16α-OH E(1) measures. Generalized linear regression models were used to assess associations between sex steroids and polymorphisms in the UGT1A and UGT2B families, SULT1A1, and SULT1E1. Women with the UGT1A1(TA7/TA7) genotype had 25% lower mean estradiol (E(2)) concentrations compared to the wildtype (TA6/TA6) (p=0.02). Similar associations were observed between SULT1A1(R213/H213) and E(1) (13% lower mean E(1) concentration vs. wildtype; p-value=0.02) and UGT2B4(E458/E458) and dehydroepiandrosterone (DHEA) (20% lower mean DHEA vs. wildtype; p-value=0.03). The SULT1E1(A/C) and the UGT1A1(TA7)-UGT1A3(R11) haplotypes were associated with reduced estrogen concentrations. Further study of UGT and SULT polymorphisms and circulating sex steroid measures in larger populations of premenopausal women is warranted.
Authors:
Mellissa Yong; Stephen M Schwartz; Charlotte Atkinson; Karen W Makar; Sushma S Thomas; Frank Z Stanczyk; Kim C Westerlind; Katherine M Newton; Victoria L Holt; Wendy M Leisenring; Johanna W Lampe
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-12-28
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  124     ISSN:  1879-1220     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-28     Completed Date:  2011-05-24     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  10-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
DNA / chemistry,  genetics
Dehydroepiandrosterone / blood*
Estradiol / blood*
Estrone / blood*
Female
Genetic Variation
Glucuronosyltransferase / blood*,  genetics*
Haplotypes
Humans
Linear Models
Middle Aged
Polymerase Chain Reaction
Polymorphism, Genetic
Premenopause / blood,  genetics
Sulfotransferases / blood*,  genetics*
Grant Support
ID/Acronym/Agency:
R01 CA097366-04/CA/NCI NIH HHS; R01CA097366/CA/NCI NIH HHS; R03 CA121872-02/CA/NCI NIH HHS; R03CA121872/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
50-28-2/Estradiol; 53-16-7/Estrone; 53-43-0/Dehydroepiandrosterone; 9007-49-2/DNA; EC 2.4.1.17/Glucuronosyltransferase; EC 2.8.2.-/Sulfotransferases
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