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Pharmacogenetics of soluble sulfotransferases (SULTs)

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Abstract

Soluble sulfotransferases (SULTs) transfer the sulfo group from the cofactor 5’-phosphoadenosine-3’-phosphosulfate (PAPS) to nucleophilic sites of relatively small acceptor molecules including various hormones and numerous xenobiotics. Sulfo conjugation of xenobiotics can lead to the formation of polar, excretable products as well as reactive, potentially mutagenic and carcinogenic metabolites. Ten SULT genes encoding 11 proteins have been identified in the human. They differ in substrate specificity and tissue distribution. Genetic polymorphisms have been detected in all human SULT genes. The functional significance of any polymorphisms that do not affect the amino acid sequence has not yet been studied. Non-synonymous single-nucleotide exchanges have been observed in SULT1A1, 1A2, 1B1, 1C1, 1C2 and 2A1. Functional consequences have primarily been explored using cDNA-expressed alloenzymes. Furthermore, an Arg213His polymorphism in SULT1A1 has a strong influence on the level of enzyme protein and activity in platelets, which have been widely used for phenotyping. Compared to other xenobiotic-metabolizing enzymes, only few studies have been conducted on associations of SULT genotypes with diseases and other health-related parameters. Statistically significant associations were observed between the SULT1A1 genotype (Arg213His) and age, obesity and certain neoplasias (mammary, pulmonary, esophageal and urothelial cancer). However, these findings require corroboration and specification. The association with neoplasias appears to be complex and varies between subgroups. This is not surprising, as SULTs are involved in the activation of some carcinogens, in the inactivation of other carcinogens, and the regulation of many hormones. It is important to study these functions of SULTs in more detail and to take into account the corresponding environmental and endogenous exposures in epidemiological studies.

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Acknowledgements

Our research on SULTs has been financially supported by the Deutsche Forschungsgemeinschaft (INK 26), Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (grant 0311243) and the European Union (grant QLK1-CT99-01197).

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Correspondence to Hansruedi Glatt.

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Glatt, H., Meinl, W. Pharmacogenetics of soluble sulfotransferases (SULTs). Naunyn-Schmiedeberg's Arch Pharmacol 369, 55–68 (2004). https://doi.org/10.1007/s00210-003-0826-0

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  • DOI: https://doi.org/10.1007/s00210-003-0826-0

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