Functionally Relevant Genetic Polymorphisms in the Human Estrogen Sulfotransferase (SULT1E1) Gene

Reference #:

2001-138

Inventors/Contributors

Richard M. Weinshilboum, M.D., Araba A. Adjei, Ph.D., Bruce W. Eckloff, Janel L. Prondzinski-Baer, Bianca A. Thomae, Eric D. Wieben, Ph.D.

Description

SULT1E1 catalyzes reactions with steroid hormones e.g. ß-Estradiol, by transferring a sulfonate group from PAPS to the hydroxy group at position 3 of the estrogen to form Estradiol 3-O-sulfate. Known substrates are estrone and estradiol, catecholestrogens and 2-Methoxyestradiol. SULT1E1 is expressed in the liver, small intestine, adrenal cortex, adrenal medulla, lung, kidney, mammary gland, ovary, endometrium, prostate, testis and epididymus. Genetic polymorphisms in SULT1E1 resulting in decreased or increased activity will cause variation in the inactivation of the estrogens. Therefore in cases such as Hormone Replacement Therapy (HRT), variations in the ability of SULT1E1 to metabolize estrogen may result in variations in response to the therapy and therefore variations in drug efficacy. Variations in the activity of SULT1E1, as a result of genetic polymorphisms may result in decreased sulfation of estrogen. The growth stimulating effect of estrogen could then be enhanced and may contribute to the processes involved with normal growth and development of the mammary glands or to tumor initiation and or promotion in breast tissue. Novel variants found have activities ranging from less than 30% to more than 300% of the wild type.

Patent Status

	U.S. Patent Number 7,288,641 Issued October 30, 2007