Human sulfotransferase (SULT) 1C1: Functional genomics of common polymorphisms

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Abstract

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.

Original languageEnglish (US)
JournalClinical Pharmacology and Therapeutics
Volume69
Issue number2
StatePublished - 2001

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Genomics
Enzymes
2-Acetylaminofluorene
Phenols
Pharmacogenetics
COS Cells
Thyroid Hormones
Gene Frequency
DNA
Genes
N-hydroxy-2-acetylaminofluorene sulfotransferase
human SULT1C2 protein
Proteins

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Human sulfotransferase (SULT) 1C1: Functional genomics of common polymorphisms",
abstract = "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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year = "2001",
language = "English (US)",
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journal = "Clinical Pharmacology and Therapeutics",
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TY - JOUR

T1 - Human sulfotransferase (SULT) 1C1

T2 - Functional genomics of common polymorphisms

AU - Freimuth, Robert

AU - Weinshilboum, Richard M

PY - 2001

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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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