title: Genetic polymorphisms and haplotype structures of the human CYP2W1 gene in a Japanese population.
abstract: A novel human cytochrome P450, designated CYP2W1, has recently been identified and is found to be present mainly in tumor cells, particularly in colon cancer cells. In the present study, we report the first systematic investigation of polymorphisms in the human CYP2W1 gene. Based on denaturing high performance liquid chromatography analyses of polymerase chain reaction products, we analyzed nine exons and exon-intron junctions of the gene in DNA samples from 200 Japanese subjects and identified six single nucleotide polymorphisms (SNP). Three of the novel nonsynonymous SNPs were as follows: 173A>C (Glu58Ala) in exon 1 and 5432G>A (Val432Ile) and 5584G>C (Gln482His) in exon 9. Two previously known nonsynonymous SNPs, that is, 2008G>A (Ala181Thr) in exon 4 and 5601C>T (Pro488Leu) in exon 9, were also found. On haplotype analyses, in addition to the wild-type CYP2W1*1A (frequency, 0.295) allele, other alleles, namely, CYP2W1*1B (0.318), CYP2W1*2 (0.005), CYP2W1*3 (0.005), CYP2W1*4 (0.008), CYP2W1*5 (0.003), and CYP2W1*6 (0.368), were also characterized. The most common allele, CYP2W1*6, exhibited the amino acid substitution Pro488Leu. These results were in good agreement with the expected genotype distributions that were calculated using the Hardy-Weinberg equation. The data on variant alleles and comprehensive haplotype structures would be useful for predicting the metabolic phenotypes of CYP2W1 substrates in the Japanese population.
authors.affiliation: Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University, 4-4-1, Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hanzawa
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Sasaki
authors.forename: Michinao
authors.initials: M
authors.lastname: Mizugaki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiratsuka
mesh_terms: D044466:Asian People; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072467:Cytochrome P450 Family 2; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C509336:CYP2W1 protein, human; D000072467:Cytochrome P450 Family 2