Human histamine n-methyltransferase gene: structural characterization and chromosomal localization

Histamine plays an important role in allergic responses and gastrointestinal acid secretion and is also a neurotransmitter. Histamine is metabolized predominantly by histamine N-methyltransferase (HNMT) and diamine oxidase. There are large individual variations in HNMT activity in the human red blood cell as a result of a common genetic polymorphism. We previously cloned a human kidney HNMT cDNA as a step toward understanding the molecular basis for this polymorphism. We now report the structural characterization and chromosomal localization of the HNMT gene, HNMT, in humans. We localized HNMTlo chromosome 2 by performing the PCR with template DNA from NIGMS Human/Rodent Somatic Cell Hybrid Mapping Panels 1 and 2. We then employed a PCR-based strategy to clone HNMT. The "long" PCR was used to amplify three overlapping gene fragments, approximately 7, 15, and 13.5 kb in length, respectively, that contained the entire gene. The template was DNA from a cell line (GM/NA10826B) that retains predominantly human chromosome 2 DNA. Site(s) of transcription initiation and lengths of 5′- and 3′-untranslated regions were determined with 5′- and 3′-RACE. HNMT is 34kb in length, and contains 6 exons that range in length from 53 to 882 bp. Intron lengths vary from 1.2 to approximately 15 kb. Structural characterization of HNMT represents an important step toward determination of the molecular basis of the pharmacogenetic regulation for this important enzyme in humans.