Human phenol sulfotransferases SULT1A2 and SULT1A1 - Genetic polymorphisms, allozyme properties, and human liver genotype-phenotype correlations

Phenol sulfotransferases (PSTs or phenol SULTs) catalyze the sulfate conjug ation of phenolic drugs, xenobiotics, and monoamines. Two human PST isoform s have been defined biochemically, a thermostable (TS), or phenol-preferrin g, and a thermolabile (TL), or monoamine-preferring form. Pharmacogenetic s tudies showed that levels of both TS PST activity and TS PST thermal stabil ity (an indirect measure of variation in amino acid sequence) in the platel et were regulated by genetic polymorphisms. Subsequent molecular genetic ex periments revealed the existence of three human PST genes, two of which, SU LT1A1 and SULT1A2, encode proteins with "TS PST-like" activity. We recently reported common nucleotide polymorphisms for SULT1A1 that are associated w ith variations in platelet TS PST activity and thermal stability. In the pr esent experiments, we set out to determine whether functionally significant DNA polymorphisms also might exist for SULT1A2, to compare the biochemical properties of all common allozymes encoded by SULT1A2 and SULT1A1, and to study phenol SULT genotype-phenotype correlations in the human liver. We ph enotyped 61 human liver biopsy samples for TS PST thermal stability and act ivity. The open reading frames of SULT1A2 and SULT1A1 then were amplified w ith the polymerase chain reaction and sequenced for each of these hepatic t issue samples. We observed 13 SULT1A2 alleles that encoded 6 allozymes. The se alleles were in linkage disequilibrium with alleles for SULT1A1. Biochem ical characterization of common allozymes encoded by both genes suggested t hat SULT1A1 was primarily responsible for "TS PST phenotype" in the human l iver. In summary, both SULT1A2 and SULT1A1 have a series of common alleles encoding enzymes that differ functionally and are associated with individua l differences in phenol SULT properties in the liver. (C) 1999 Elsevier Sci ence Inc.