Identification of 197 genetic variations in six human methyltransferase genes in the Japanese population

Methylation is an important event in the biotransformation pathway for many drugs and xenobiotic compounds. We screened DNA from 48 Japanese individua ls for single-nucleotide polymorphisms (SNPs) in six methyltransferase (MT) genes (catechol-O-MT, COMT, guanidinoacetate N-MT, GAMT; histamine N-MT, H NMT, nicotinamide N-MT, NNMT; phosphatidylethanolamine N-MT, PEMT; and phen ylethanolamine N-MT, PNMT) by direct sequencing of their entire genomic reg ions except for repetitive elements. This approach identified 190 SNPs and seven insertion/deletion polymorphisms among the six genes. Of the 190 SNPs , 33 were identified in the COMT gene, 6 in GAMT, 41 in HNMT, 8 in NNMT, 98 in PEMT, and 4 in PNMT. Nine were located in 5' Ranking regions, 156 in in trons, 10 in exons, and 15 in 3' flanking regions. These variants may contr ibute to a more precise understanding of possible correlations between geno types and disease-susceptibility phenotypes or risk for side effects from d rugs.