Five novel single nucleotide polymorphisms in the CYP2C8 gene, one of which induces a frame-shift

Akiko Soyama; Yoshiro Saito; Kazuo Komamura; Kazuyuki Ueno; Shiro Kamakura; Shogo Ozawa; Jun-ichi Sawada

doi:10.2133/dmpk.17.374

Five novel single nucleotide polymorphisms in the CYP2C8 gene, one of which induces a frame-shift

Drug Metab Pharmacokinet. 2002;17(4):374-7. doi: 10.2133/dmpk.17.374.

Authors

Akiko Soyama¹, Yoshiro Saito, Kazuo Komamura, Kazuyuki Ueno, Shiro Kamakura, Shogo Ozawa, Jun-ichi Sawada

Affiliation

¹ Project team for Pharmacogenetics, National Institute of Health Sciences, Tokyo, Japan.

PMID: 15618689
DOI: 10.2133/dmpk.17.374

Abstract

Five novel single nucleotide polymorphisms (SNPs) were found in exon 3 and introns 1, 3, 7, and 8 in cytochrome P450 (CYP) 2C8 gene from 54 Japanese individuals, who were administered the anti-arrhythmic drug amiodarone. The detected SNPs were as follows: 1) SNP, MPJ6_2C8014; GENE NAME, CYP2C8; ACCESSION NUMBER, NT_008769; LENGTH, 25 bases; 5'-ATTCAGAAATATC/TGAATCTATGTGT-3' 2) SNP, MPJ6_2C8015; GENE NAME, CYP2C8; ACCESSION NUMBER, NM_000770 and NT_008769; LENGTH, 25 bases; 5'-GGAGGAGTTGAGA/-AAAACCAAGGGT-3'. 3) SNP, MPJ6_2C8016; GENE NAME, CYP2C8; ACCESSION NUMBER, NT_008769; LENGTH, 25 bases; 5'-ATTTGTAAGATAT/-TGTTTAAAATTT-3' 4) SNP, MPJ6_2C8017; GENE NAME, CYP2C8; ACCESSION NUMBER, NT_008769; LENGTH, 25 bases; 5'-TTGGTTCCAACCC/TTCTAACAACACA-3' 5) SNP, MPJ6_2C8018; GENE NAME, CYP2C8; ACCESSION NUMBER, NT_008769; LENGTH, 25 bases; 5'-GATAGCAAATATA/GTCTCTTTTTGTA-3' Among these SNPs, MPJ6_2C8015 was expected to cause a frame-shift due to the deletion of adenine 471, resulting in amino acid alterations from codon 159 and an early stop codon at residue 177. Therefore, the variant enzyme is most likely to be inactive since it lacks 64% of the protein structure, including the heme-binding site and 5 out of 6 substrate recognition sites.