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

• Published in: Journal of human genetics Vol. 46; no. 9; pp. 529 - 537
• Main Authors: Saito, S., Iida, A., Sekine, A., Miura, Y., Sakamoto, T., Ogawa, C., Kawauchi, S., Higuchi, S., Nakamura, Y.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.09.2001
• Subjects: Biotransformation; Catechol; Catechol O-methyltransferase; DNA methylation; Exons; Genetic diversity; Histamine; Insertion; Introns; Methyltransferase; Nicotinamide; Phenotypes; Phosphatidylethanolamine; Single-nucleotide polymorphism
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1007/s100380170035

Methylation is an important event in the biotransformation pathway for many drugs and xenobiotic compounds. We screened DNA from 48 Japanese individuals for single-nucleotide polymorphisms (SNPs) in six methyltransferase (MT) genes (catechol-O-MT, COMT; guanidinoacetate N-MT, GAMT; histamine N-MT, HNMT; nicotinamide N-MT, NNMT; phosphatidylethanolamine N-MT, PEMT; and phenylethanolamine N-MT, PNMT) by direct sequencing of their entire genomic regions 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′ flanking regions, 156 in introns, 10 in exons, and 15 in 3′ flanking regions. These variants may contribute to a more precise understanding of possible correlations between genotypes and disease-susceptibility phenotypes or risk for side effects from drugs.