TY - JOUR
T1 - Human sulfotransferase (SULT) 1C1
T2 - Functional genomics of common polymorphisms
AU - Freimuth, R. R.
AU - Weinshilboum, R. M.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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M3 - Article
AN - SCOPUS:33748965939
SN - 0009-9236
VL - 69
SP - P32
JO - Clinical pharmacology and therapeutics
JF - Clinical pharmacology and therapeutics
IS - 2
ER -