SULT1C1 catalyzes the sulfation of planar phenols, thyroid hormones and the chemical procarcinogen N-OH-2-acetylaminofluorene in a step required for the metabolic activation of that compound. We recently cloned the human SULT1C1 gene and resequenced it using DNA from 89 Caucasian subjects. A total of 31 polymorphisms were found, including 7 nonsynonymous cSNPs, 4 of which had allele frequencies greater than 1%. To study the effects of these cSNPs on enzyme activity and/or quantity of immunoreactive protein, expression constructs were created, and those constructs were used to transfect COS-1 cells. With 4-nitrophenol as a substrate, Asp60Ala and Arg73Gln had only about 15% of the activity of the wild type (WT) enzyme. Ser111Phe had no detectable enzyme activity, and Phe193Leu had approximately 40% of that of the WT sequence. Functional genomic characterization of cSNPs for SULT1C1 will now make it possible to use these pharmacogenomic data to test clinically relevant hypotheses.
|Clinical pharmacology and therapeutics
|Published - 2001
ASJC Scopus subject areas
- Pharmacology (medical)