Human histamine N-methyltransferase pharmacogenetics: common genetic polymorphisms that alter activity

Histamine N-methyltransferase (HNMT) catalyzes a major path-way in histamine metabolism. Levels of HNMT activity in hu-mans are regulated by inheritance. We set out to study the molecular basis for this genetic regulation. Northern blot anal-ysis showed that HNMT is highly expressed in the kidney, so we determined levels of enzyme activity and thermal stability in 127 human renal biopsy samples. DNA was isolated from 12 kidney samples with widely different HNMT phenotypes, and exons of the HNMT gene were amplified with the polymerase chain reaction. In these 12 samples, we observed a C314T transition that resulted in a Thr105Ile change in encoded amino acid, as well as an A939G transition within the 39-untranslated region. All remaining renal biopsy samples then were geno-typed for these two variant sequences. Frequencies of th