SULT1A1 and 1A2 Pharmacogenomics

Reference #:

1998-071

Inventors/Contributors

Richard M. Weinshilboum, M.D., Diane M. Otterness, Jon A. Van Loon, M.D., Rebecca B. Raftogianis, Ph.D., Thomas C. Wood

Description

Substrates for SULT1A1 are; 4-nitrophenol, 17beta-estradiol (E2), diethylstilboestrol (DES), 1-naphol, 4-hydroxytamoxifen, minoxidil, estrone (E1), epinephrine, dopamine, acetaminophen, genistein, other monocyclic phenols. The gene is ubiquitously expressed but especially prominent in liver but also lung, brain, platelet, prostate, placenta, and adrenal gland. Diseases associated with increased or decreased activity of SULT1A1 are breast cancer, prostate cancer, colon cancer, lung cancer, and esophageal cancer. Pending divisional application 09/839,545 with claims for determining risk estimate of cancer by detect the presence or absence of a nucleotide variant that encodes a SULT1A1 polypeptide having a histine at residue 213. The 213 variant has significantly reduced enzyme activity and 3 studies to date have shown it to be correlated with cancer. Substrates for SULT1A2 are; 4-nitrophenol, 17beta-estradiol (E2), diethylstilboestrol (DES), 1-naphol, 4-hydroxytamoxifen, minoxidil, estrone (E1), epinephrine, dopamine, acetaminophen, genistein, other monocyclic phenols. Diseases that might be associated with increased or decreased activity of SULT1A2 are steroid hormone dependent such as cancers. Issued patent US#6,265,561 with claims to SULT1A2*4, SULT1A2*5 and SULT1A2*6. Studies have shown that SULT1A2*6 results in a protein with a dramatically lower affinity for the SULT1A2 substrate 4-nitrophenol.

Patent Status

	U.S. Patent Number 6,265,561 Issued July 24, 2001