Pharmacogenetics of soluble sulfotransferases (SULTs).
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.
Department of Toxicology, German Institute of Human Nutrition (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Potsdam-Rehbrücke, Germany. glatt@mail.dife.de
Hansruedi
H
Glatt
Walter
W
Meinl
D000818:Animals; D001711:Biotransformation / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012995:Solubility; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000235:genetics*; D015262:Xenobiotics / Q000493:pharmacokinetics*
D007527:Isoenzymes; D015262:Xenobiotics; D015238:Sulfotransferases