TY - JOUR
T1 - Phenol sulfotransferase pharmacogenetics in humans
T2 - Association of common SULT1A1 alleles with TS PST phenotype
AU - Raftogianis, Rebecca B.
AU - Wood, Thomas C.
AU - Otterness, Diane M.
AU - Van Loon, Jon A.
AU - Weinshilboum, Richard M.
N1 - Funding Information:
1Supported in part by NIH Grants RO1 GM 28157 (R.M.W.) and RO1 GM 35720 (R.M.W.), by a supplement to RO1 GM 35720 supported by the Of®ce of Research on Women's Health (R.M.W.), and by an NRSA (NIH) Individual Postdoctoral Fellowship (R.B.R.). 2Correspondence and reprint requests. Fax: (507) 284-9111.
PY - 1997/10/9
Y1 - 1997/10/9
N2 - 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.
AB - 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.
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U2 - 10.1006/bbrc.1997.7466
DO - 10.1006/bbrc.1997.7466
M3 - Article
C2 - 9345314
AN - SCOPUS:0031561408
SN - 0006-291X
VL - 239
SP - 298
EP - 304
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -