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Background/Aims SULT1A3 catalyzes the sulfate conjugation of catecholamines and structurally related drugs. Following completion of the Human Genome Project, it appeared that SULT1A3: might be duplicated. The purpose of this study was to verify and characterize this gene duplication. Methods PCR-based assays and FISH were used to verify that 2 SULT1A3 genes are present on chromosome 16. Reanalysis of previous gene resequencing data was performed to confirm the presence of SULT1A3: SNPs identified previously and also to identify novel polymorphisms. Functional genomic studies were performed on 3 novel cSNPS to determine levels of SULT1A3 activity enzyme activity, immunoreactive protein and substrate kinetics. RT-PCR was used to determine if both SULT1A3: copies are transcriptionally active. Results Two copies of SULT1A3: are present on chromosome 16. All previously reported SNPs were confirmed, and 11 novel SNPs were identified. Both genes can produce mRNA transcripts and functional genomic studies showed that 2 novel cSNPs resulted in decreased activity and levels of protein. Conclusions The duplication of SULT1A3: will have to be taken into account during future efforts to understand individual variation in SULT1A3 activity or properties. Clinical Pharmacology & Therapeutics (2005) 77, P23–P23; doi: 10.1016/j.clpt.2004.11.090

PNMT (EC 2.1.1.28) catalyzes the N-methylation of norepinephrine to form epinephrine. We set out to resequence the human PNMT gene, including all exons and introns as well as approximately 1 kb of the 5′-flanking region using Coriell Institute DNA samples from 60 African-American (AA) and 60 Caucasian-American (CA) subjects. Within the 3.5 kb resequenced, 17 single nucleotide polymorphisms (SNPs) were observed, including 3 nonsynonymous cSNPs (Asn9Ser, Thr98Ala and Arg112Cys). When constructs for the nonsynonymous cSNPs were transiently expressed in COS-1 cells, the Ala98 allozyme displayed virtually no enzyme activity or immunoreactive protein when compared with the wild type (WT) allozyme (P