Human SULT1A3 pharmacogenetics: Gene duplication and functional genomic studies

Michelle A T Hildebrandt, Oreste E. Salavaggione, Yvette N. Martin, Heather C. Flynn, Syed Jalal, Eric D Wieben, Richard M Weinshilboum

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Sulfotransferase (SULT) 1A3 catalyzes the sulfate conjugation of catecholamines. Inheritance is an important factor responsible for individual variation in SULT1A3 activity, and gene resequencing studies have shown the presence of one functionally significant SULT1A3 nonsynonymous cSNP. However, following completion of the Human Genome Project, it appeared that SULT1A3 might be duplicated. We used specific PCR-based assays and fluorescence in situ hybridization to verify that 2 SULT1A3 genesa - SULT1A3 and SULT1A4 - were present on chromosome 16 in all human DNA samples studied. Furthermore, reanalysis of previous gene resequencing data confirmed the presence of the SULT1A3 SNPs identified previously, but also revealed 11 novel polymorphisms, including 3 nonsynonymous cSNPs. Functional genomic studies showed that two of those cSNPs, C302T, and C302A, resulted in decreased enzyme activity without striking changes in substrate kinetics but with parallel changes in levels of immunoreactive protein. In addition, RT-PCR revealed that both SULT1A3 and SULT1A4 can be transcriptionally active. The duplication of SULT1A3 will have to be taken into account in future efforts to understand individual variation in SULT1A3 activity or properties.

Original languageEnglish (US)
Pages (from-to)870-878
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume321
Issue number4
DOIs
StatePublished - Sep 3 2004

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Keywords

  • Functional genomics
  • Gene duplication
  • Genetic polymorphism
  • Pharmacogenetics
  • SNPs
  • Sulfotransferase
  • SULT1A3
  • SULT1A4

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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