TY - JOUR
T1 - Associations between polymorphisms in glucuronidation and sulfation enzymes and sex steroid concentrations in premenopausal women in the United States
AU - Yong, Mellissa
AU - Schwartz, Stephen M.
AU - Atkinson, Charlotte
AU - Makar, Karen W.
AU - Thomas, Sushma S.
AU - Stanczyk, Frank Z.
AU - Westerlind, Kim C.
AU - Newton, Katherine M.
AU - Holt, Victoria L.
AU - Leisenring, Wendy M.
AU - Lampe, Johanna W.
PY - 2011/3
Y1 - 2011/3
N2 - 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 16 alpha-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. (C) 2010 Elsevier Ltd. All rights reserved.
AB - 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 16 alpha-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. (C) 2010 Elsevier Ltd. All rights reserved.
U2 - 10.1016/j.jsbmb.2010.12.014
DO - 10.1016/j.jsbmb.2010.12.014
M3 - Article (Academic Journal)
C2 - 21193038
SN - 0960-0760
VL - 124
SP - 10
EP - 18
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
IS - 1-2
ER -