Genetic variation, expression and ontogeny of sulfotransferase SULT2A1 in humans

Abstract

Sulfotransferases (SULTs) are enzymes involved in the metabolism of several endogenous molecules. The activity and expression exhibit inter- and intra-individual variations due to age and genetic variation. The aims of this study were to compare the gene expression of SULT2A1 in fetal and adult livers, to study the intra-individual tissue distribution, and investigate if expression is associated with a SULT2A1 copy number variation polymorphism. In contrast to other drug metabolizing enzyme systems the expression of SULT2A1 did not differ between fetal and adult liver samples and it was not affected by maternal smoking or gestational age. Gene expression in relation to sex could not be assessed as the sex of the fetuses was unknown. SULT2A1 was consistently expressed in livers and adrenals, being seven times more abundant in adrenals, but was absent in the lungs. The SULT2A1 copy number variation was proportional to gene expression in liver and adrenals. Our results show that SULT2A1 is important in the first trimester; particularly in the adrenals.

Liver Expression of Sulphotransferase 2A1 Enzyme Is Impaired in Patients with Primary Sclerosing Cholangitis: Lack of the Response to Enhanced Expression of PXR

“…Since most of the accessible research in this area was undertaken in a rodent model, which does not translate directly to humans, our data on PXR and SULT2A1 expressions in humans are novel and may have a future translational clinical repercussion. More research is needed to understand the enigmatic role of SULT2A1 in the development of liver disease [ 29 , 30 ].…”

Polymorphic Human Sulfotransferase 2A1 Mediates the Formation of 25-Hydroxyvitamin D3-3-O-Sulfate, a Major Circulating Vitamin D Metabolite in Humans

“…region of the SULT2A1 gene) and that rs296361 has no causal effect on the SULT2A1 phenotype. It is important to note that a copy number variation (CNV) in the SULT2A1 gene locus has also been described (Ekström and Rane, 2015) and has been associated with the urinary excretion of DHEA-sulfate and testosterone-sulfate (Schulze et al, 2013). However, the frequency of the CNV appears to be much lower than that of rs296361.…”

SULFATION PATHWAYS: Insights into steroid sulfation and desulfation pathways

“…Finally, it is population genetics influencing steroid sulfation pathways and the interindividual variability in drug response. Several coding SNPs in SULT genes influence an individual's sulfation capacity (Louwers et al 2013), but also gene number variations have been reported for SULT2A1 (Ekstrom & Rane 2015) and other sulfotransferases (Marto et al 2017). In fact, the SULT2A1 gene seems to be more evolvable than, for example, PAPS synthases (Mueller et al 2015); Ensembl (https:// www.ensembl.org) lists various expansions of this gene in different lineages with an eight-genes-comprising gene cluster in mice (Zerbino et al 2018), while a set of two PAPS synthase genes is highly conserved in vertebrates (van den Boom et al 2012).…”