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. 1999 Jan 1;337(Pt 1):45–49.

Phenol sulphotransferase SULT1A1 polymorphism: molecular diagnosis and allele frequencies in Caucasian and African populations.

M W Coughtrie 1, R A Gilissen 1, B Shek 1, R C Strange 1, A A Fryer 1, P W Jones 1, D E Bamber 1
PMCID: PMC1219934  PMID: 9854023

Abstract

Sulphation, catalysed by members of the sulphotransferase (SULT) enzyme family, is an important component of the body's chemical defence mechanism, but also acts to bioactivate mutagens such as hydroxylated aryl and heterocyclic amines. A major human sulphotransferase, SULT1A1 (P-PST), metabolizes and/or bioactivates many drugs, iodothyronines and hydroxylated aromatic amines. The enzyme activity varies widely within the population and is under genetic control. We have developed an assay detecting a G-->A transition in SULT1A1 that causes an Arg213-->His substitution associated with low SULT activity and altered enzyme properties, and have used it to assess the SULT1A1 genotype in Caucasian (n=293) and African (Nigerian, n=52) populations. We show that the mutant SULT1A1*2 allele is present at frequencies of 0.321 and 0.269 in the Caucasian and African populations respectively. We also demonstrate a significant age-related difference in SULT1A1 genotype within our Caucasian population, with increasing incidence of SULT1A1*1 homozygosity and decreasing incidence of SULT1A1*2 homozygosity with increasing age, indicating a potential association of SULT1A1*1 allozyme(s) with protection against cell and/or tissue damage during aging.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aklillu E., Persson I., Bertilsson L., Johansson I., Rodrigues F., Ingelman-Sundberg M. Frequent distribution of ultrarapid metabolizers of debrisoquine in an ethiopian population carrying duplicated and multiduplicated functional CYP2D6 alleles. J Pharmacol Exp Ther. 1996 Jul;278(1):441–446. [PubMed] [Google Scholar]
  2. Bernier F., Soucy P., Luu-The V. Human phenol sulfotransferase gene contains two alternative promoters: Structure and expression of the gene. DNA Cell Biol. 1996 May;15(5):367–375. doi: 10.1089/dna.1996.15.367. [DOI] [PubMed] [Google Scholar]
  3. Boberg E. W., Miller E. C., Miller J. A., Poland A., Liem A. Strong evidence from studies with brachymorphic mice and pentachlorophenol that 1'-sulfoöxysafrole is the major ultimate electrophilic and carcinogenic metabolite of 1'-hydroxysafrole in mouse liver. Cancer Res. 1983 Nov;43(11):5163–5173. [PubMed] [Google Scholar]
  4. Chou H. C., Lang N. P., Kadlubar F. F. Metabolic activation of N-hydroxy arylamines and N-hydroxy heterocyclic amines by human sulfotransferase(s). Cancer Res. 1995 Feb 1;55(3):525–529. [PubMed] [Google Scholar]
  5. Coughtrie M. W., Sharp S., Maxwell K., Innes N. P. Biology and function of the reversible sulfation pathway catalysed by human sulfotransferases and sulfatases. Chem Biol Interact. 1998 Feb 20;109(1-3):3–27. doi: 10.1016/s0009-2797(97)00117-8. [DOI] [PubMed] [Google Scholar]
  6. Davis W., Venitt S., Phillips D. H. The metabolic activation of tamoxifen and alpha-hydroxytamoxifen to DNA-binding species in rat hepatocytes proceeds via sulphation. Carcinogenesis. 1998 May;19(5):861–866. doi: 10.1093/carcin/19.5.861. [DOI] [PubMed] [Google Scholar]
  7. Dooley T. P., Huang Z. Genomic organization and DNA sequences of two human phenol sulfotransferase genes (STP1 and STP2) on the short arm of chromosome 16. Biochem Biophys Res Commun. 1996 Nov 1;228(1):134–140. doi: 10.1006/bbrc.1996.1628. [DOI] [PubMed] [Google Scholar]
  8. Dooley T. P., Obermoeller R. D., Leiter E. H., Chapman H. D., Falany C. N., Deng Z., Siciliano M. J. Mapping of the phenol sulfotransferase gene (STP) to human chromosome 16p12.1-p11.2 and to mouse chromosome 7. Genomics. 1993 Nov;18(2):440–443. doi: 10.1006/geno.1993.1494. [DOI] [PubMed] [Google Scholar]
  9. Falany C. N. Molecular enzymology of human liver cytosolic sulfotransferases. Trends Pharmacol Sci. 1991 Jul;12(7):255–259. doi: 10.1016/0165-6147(91)90566-b. [DOI] [PubMed] [Google Scholar]
  10. Gilissen R. A., Bamforth K. J., Stavenuiter J. F., Coughtrie M. W., Meerman J. H. Sulfation of aromatic hydroxamic acids and hydroxylamines by multiple forms of human liver sulfotransferases. Carcinogenesis. 1994 Jan;15(1):39–45. doi: 10.1093/carcin/15.1.39. [DOI] [PubMed] [Google Scholar]
  11. Glatt H. Sulfation and sulfotransferases 4: bioactivation of mutagens via sulfation. FASEB J. 1997 Apr;11(5):314–321. doi: 10.1096/fasebj.11.5.9141497. [DOI] [PubMed] [Google Scholar]
  12. Hwang S. R., Kohn A. B., Hook V. Y. Molecular cloning of an isoform of phenol sulfotransferase from human brain hippocampus. Biochem Biophys Res Commun. 1995 Feb 15;207(2):701–707. doi: 10.1006/bbrc.1995.1244. [DOI] [PubMed] [Google Scholar]
  13. Jones A. L., Hagen M., Coughtrie M. W., Roberts R. C., Glatt H. Human platelet phenolsulfotransferases: cDNA cloning, stable expression in V79 cells and identification of a novel allelic variant of the phenol-sulfating form. Biochem Biophys Res Commun. 1995 Mar 17;208(2):855–862. doi: 10.1006/bbrc.1995.1414. [DOI] [PubMed] [Google Scholar]
  14. Jones A. L., Roberts R. C., Coughtrie M. W. The human phenolsulphotransferase polymorphism is determined by the level of expression of the enzyme protein. Biochem J. 1993 Dec 1;296(Pt 2):287–290. doi: 10.1042/bj2960287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kakuta Y., Pedersen L. G., Carter C. W., Negishi M., Pedersen L. C. Crystal structure of estrogen sulphotransferase. Nat Struct Biol. 1997 Nov;4(11):904–908. doi: 10.1038/nsb1197-904. [DOI] [PubMed] [Google Scholar]
  16. Kalow W. Interethnic variation of drug metabolism. Trends Pharmacol Sci. 1991 Mar;12(3):102–107. doi: 10.1016/0165-6147(91)90516-u. [DOI] [PubMed] [Google Scholar]
  17. Miller J. A. Sulfonation in chemical carcinogenesis--history and present status. Chem Biol Interact. 1994 Jun;92(1-3):329–341. doi: 10.1016/0009-2797(94)90074-4. [DOI] [PubMed] [Google Scholar]
  18. Ozawa S., Nagata K., Shimada M., Ueda M., Tsuzuki T., Yamazoe Y., Kato R. Primary structures and properties of two related forms of aryl sulfotransferases in human liver. Pharmacogenetics. 1995;5(Spec No):S135–S140. doi: 10.1097/00008571-199512001-00015. [DOI] [PubMed] [Google Scholar]
  19. Ozawa S., Nagata K., Yamazoe Y., Kato R. Formation of 2-amino-3-methylimidazo[4,5-f]quinoline- and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline-sulfamates by cDNA-expressed mammalian phenol sulfotransferases. Jpn J Cancer Res. 1995 Mar;86(3):264–269. doi: 10.1111/j.1349-7006.1995.tb03049.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ozawa S., Tang Y. M., Yamazoe Y., Kato R., Lang N. P., Kadlubar F. F. Genetic polymorphisms in human liver phenol sulfotransferases involved in the bioactivation of N-hydroxy derivatives of carcinogenic arylamines and heterocyclic amines. Chem Biol Interact. 1998 Feb 20;109(1-3):237–248. doi: 10.1016/s0009-2797(97)00135-x. [DOI] [PubMed] [Google Scholar]
  21. Price R. A., Spielman R. S., Lucena A. L., Van Loon J. A., Maidak B. L., Weinshilboum R. M. Genetic polymorphism for human platelet thermostable phenol sulfotransferase (TS PST) activity. Genetics. 1989 Aug;122(4):905–914. doi: 10.1093/genetics/122.4.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Probst-Hensch N. M., Haile R. W., Ingles S. A., Longnecker M. P., Han C. Y., Lin B. K., Lee D. B., Sakamoto G. T., Frankl H. D., Lee E. R. Acetylation polymorphism and prevalence of colorectal adenomas. Cancer Res. 1995 May 15;55(10):2017–2020. [PubMed] [Google Scholar]
  23. Raftogianis R. B., Her C., Weinshilboum R. M. Human phenol sulfotransferase pharmacogenetics: STP1 gene cloning and structural characterization. Pharmacogenetics. 1996 Dec;6(6):473–487. doi: 10.1097/00008571-199612000-00001. [DOI] [PubMed] [Google Scholar]
  24. Raftogianis R. B., Wood T. C., Otterness D. M., Van Loon J. A., Weinshilboum R. M. Phenol sulfotransferase pharmacogenetics in humans: association of common SULT1A1 alleles with TS PST phenotype. Biochem Biophys Res Commun. 1997 Oct 9;239(1):298–304. doi: 10.1006/bbrc.1997.7466. [DOI] [PubMed] [Google Scholar]
  25. Stephens E. A., Taylor J. A., Kaplan N., Yang C. H., Hsieh L. L., Lucier G. W., Bell D. A. Ethnic variation in the CYP2E1 gene: polymorphism analysis of 695 African-Americans, European-Americans and Taiwanese. Pharmacogenetics. 1994 Aug;4(4):185–192. doi: 10.1097/00008571-199408000-00002. [DOI] [PubMed] [Google Scholar]
  26. Surh Y. J., Tannenbaum S. R. Sulfotransferase-mediated activation of 7,8,9,10-tetrahydro-7-ol, 7,8-dihydrodiol, and 7,8,9,10-tetraol derivatives of benzo[a]pyrene. Chem Res Toxicol. 1995 Jul-Aug;8(5):693–698. doi: 10.1021/tx00047a008. [DOI] [PubMed] [Google Scholar]
  27. Van Loon J., Weinshilboum R. M. Human platelet phenol sulfotransferase: familial variation in thermal stability of the TS form. Biochem Genet. 1984 Dec;22(11-12):997–1014. doi: 10.1007/BF00499627. [DOI] [PubMed] [Google Scholar]
  28. Weinshilboum R. M., Otterness D. M., Aksoy I. A., Wood T. C., Her C., Raftogianis R. B. Sulfation and sulfotransferases 1: Sulfotransferase molecular biology: cDNAs and genes. FASEB J. 1997 Jan;11(1):3–14. [PubMed] [Google Scholar]
  29. Weinshilboum R. Sulfotransferase pharmacogenetics. Pharmacol Ther. 1990;45(1):93–107. doi: 10.1016/0163-7258(90)90010-y. [DOI] [PubMed] [Google Scholar]
  30. Wilborn T. W., Comer K. A., Dooley T. P., Reardon I. M., Heinrikson R. L., Falany C. N. Sequence analysis and expression of the cDNA for the phenol-sulfating form of human liver phenol sulfotransferase. Mol Pharmacol. 1993 Jan;43(1):70–77. [PubMed] [Google Scholar]
  31. Zhao L., Alldersea J., Fryer A., Tighe A., Ollier B., Thomson W., Jones P., Strange R. Polymorphism at the glutathione S-transferase GSTM1 locus: a study of the frequencies of the GSTM1 A, B, A/B and null phenotypes in Nigerians. Clin Chim Acta. 1994 Feb;225(1):85–88. doi: 10.1016/0009-8981(94)90032-9. [DOI] [PubMed] [Google Scholar]
  32. Zhu X., Veronese M. E., Bernard C. C., Sansom L. N., McManus M. E. Identification of two human brain aryl sulfotransferase cDNAs. Biochem Biophys Res Commun. 1993 Aug 31;195(1):120–127. doi: 10.1006/bbrc.1993.2018. [DOI] [PubMed] [Google Scholar]
  33. van de Poll M. L., Tijdens R. B., Vondrácek P., Bruins A. P., Meijer D. K., Meerman J. H. The role of sulfation in the metabolic activation of N-hydroxy-4'-fluoro-4-acetylaminobiphenyl. Carcinogenesis. 1989 Dec;10(12):2285–2291. doi: 10.1093/carcin/10.12.2285. [DOI] [PubMed] [Google Scholar]

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