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Accessible Unlicensed Requires Authentication Published by De Gruyter September 21, 2011

A common CYP1B1 polymorphism is associated with 2-OHE1/16-OHE1 urinary estrone ratio

Valentina Paracchini, Paola Pedotti, Sara Raimondi, Seymour Garte, H. Leon Bradlow, Daniel W. Sepkovic and Emanuela Taioli

Abstract

Cytochrome P450 (CYP) is a multigene family of enzymes involved in important life functions; some of these genes are inducible and are implicated in the oxidative metabolic activation and detoxification of many endogenous and exogenous compounds. CYP1B1 codes for an enzyme that catalyses the production of a 2- and 4-hydroxyl group in estrone and estradiol, while CYP1A1 catalyzes the 2-hydroxylation of estradiol in endometrium. The two genes were evaluated in a cohort of 150 subjects: African-American women had significantly lower 2-hydroxyl estrone/16-hydroxyl estrone (2-OHE1/16-OHE1) urinary metabolite ratios than Caucasian women (2.06±1.05 vs. 1.43±0.56; p=0.0002). A common polymorphism in the CYP1B1 gene (leucine to valineat codon 432) was associated with changes in urinary estrogen levels: both Caucasian and African-American women carrying the variant allele showed higher urinary metabolite ratios than women with the wild-type allele. No effect of the CYP1A1 MspI was observed. The 4-OHE1/2-OHE1 ratio was lower in subjects carrying the variant allele (Leu). The percentage change in 2-OHE1/16-OHE1 urinary ratio after indole treatment was significant in both Caucasian and African-American women carrying the wild-type CYP1B1 genotype, although it was more evident in African-Americans than in Caucasians. These results suggest that the Leu/Val CYP1B1 polymorphism may modify estradiol metabolism.


Corresponding author: Emanuela Taioli, MD PhD, Molecular and Genetic Epidemiology Unit, Fondazione Ospedale Policlinico IRCCS, Palazzina Bertarelli, Via Pace 9, 20122 Milano, Italy Phone/Fax: +39-02-55034055,

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Received: 2005-4-19
Accepted: 2005-4-25
Published Online: 2011-9-21
Published in Print: 2005-7-1

©2005 by Walter de Gruyter Berlin New York