Phenol sulfotransferase pharmacogenetics in humans: Association of common SULT1A1 alleles with TS PST phenotype

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

Research output: Contribution to journalArticle

249 Citations (Scopus)

Abstract

The phenol sulfotransferases (PSTs) catalyze the sulfation of both small planar phenols and phenolic monoamines. Three highly homologous PST genes, SULT1A1, SULT1A2, and SULT1A3, are known to exist in humans. The prototypic biochemical phenotype associated with the enzyme encoded by SULT1A1 is the thermal stable (TS) sulfation of 4 μM 4-nitrophenol (TS PST activity). Biochemical pharmacogenetic studies have demonstrated that individual variation in both TS PST activity and thermal stability in humans are inherited. As a step toward understanding molecular mechanisms responsible for the genetic regulation of PSTs in humans, we report here common SULT1A1 nucleotide polymorphisms that are associated with phenotypic variation in both platelet TS PST activity and thermal stability. When 905 human subjects were phenotyped for platelet TS PST activity and thermal stability, activity varied more than 50-fold, and thermal stability varied over 10-fold. DNA was isolated from the blood of 33 of these subjects selected on the basis of 'extreme' TS PST phenotypes: high activity and high thermal stability; low activity and low thermal stability; or low activity and high thermal stability. These 33 subjects were genotyped for SULT1A1 by PCR amplification and sequencing of the entire open reading frame (ORF) as well as approximately 1 kb of intron DNA sequence. One common allele, SULT1A1(*)2, was uniformly associated with both very low TS PST activity and low thermal stability. The allele frequency of SULT1A1(*)2 in a randomly selected population sample of 150 Caucasian blood donors was 0.31 (31%), indicating that approximately 9% of this population would be homozygous for that allele.

Original languageEnglish (US)
Pages (from-to)298-304
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume239
Issue number1
DOIs
StatePublished - Oct 9 1997

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Arylsulfotransferase
Pharmacogenetics
Hot Temperature
Alleles
Thermodynamic stability
Phenotype
Thermodynamic properties
Platelets
Blood
Phenols
DNA sequences
Extreme Heat
Blood Platelets
Polymorphism
Introns
Amplification
Nucleotides
Genes

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Phenol sulfotransferase pharmacogenetics in humans : Association of common SULT1A1 alleles with TS PST phenotype. / Raftogianis, Rebecca B.; Wood, Thomas C.; Otterness, Diane M.; Van Loon, Jon A.; Weinshilboum, Richard M.

In: Biochemical and Biophysical Research Communications, Vol. 239, No. 1, 09.10.1997, p. 298-304.

Research output: Contribution to journalArticle

Raftogianis, Rebecca B. ; Wood, Thomas C. ; Otterness, Diane M. ; Van Loon, Jon A. ; Weinshilboum, Richard M. / Phenol sulfotransferase pharmacogenetics in humans : Association of common SULT1A1 alleles with TS PST phenotype. In: Biochemical and Biophysical Research Communications. 1997 ; Vol. 239, No. 1. pp. 298-304.
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