SULT genetic polymorphisms: physiological, pharmacological and clinical implications

Abstract

Introduction

Cytosolic sulfotransferases (SULTs)-mediated sulfation is critically involved in the metabolism of key endogenous compounds, such as catecholamines and thyroid/steroid hormones, as well as a variety of drugs and other xenobiotics. Studies performed in the past three decades have yielded a good understanding about the enzymology of the SULTs and their structural biology, phylogenetic relationships, tissue/organ-specific/developmental expression, as well as the regulation of the SULT gene expression. An emerging area is related to the functional impact of the SULT genetic polymorphisms.

Areas covered

The current review aims to summarize our current knowledge about the above-mentioned aspects of the SULT research. An emphasis is on the information concerning the effects of the polymorphisms of the SULT genes on the functional activity of the SULT allozymes and the associated physiological, pharmacological, and clinical implications.

Expert opinion

Elucidation of how SULT SNPs may influence the drug-sulfating activity of SULT allozymes will help understand the differential drug metabolism and eventually aid in formulating personalized drug regimens. Moreover, the information concerning the differential sulfating activities of SULT allozymes toward endogenous compounds may allow for the development of strategies for mitigating anomalies in the metabolism of these endogenous compounds in individuals with certain SULT genotypes.

Keywords:

• Cytosolic sulfotransferase
• SULT
• sulfation
• single-nucleotide polymorphism
• SNP

Article highlights

• Cytosolic sulfotransferases (SULTs)-mediated sulfation is critically involved in the metabolism of key endogenous compounds, such as catecholamines and steroid/thyroid hormones, as well as drugs and other xenobiotics.

• In humans, 18 SULT genes, including five pseudogenes, have been identified and classified into five gene families.

• Like many other genes, single nucleotide polymorphisms (SNPs) occur for genes encoding the SULTs.

• Studies have shown that certain SULT genotypes may predispose risks for diseases.

• SULT allozymes, coded by distinct SULT genotypes, have been reported to display differential sulfating activities.

• Elucidation of the functional relevance of SULT SNPs may eventually aid in formulating personalized drug regimens and help develop strategies for mitigating anomalies in the metabolism of key endogenous compounds.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript received NIH funding (grant number: R03HD071146).