title: Single nucleotide polymorphisms and haplotypes of CYP1A2 in a Japanese population.
abstract: In order to identify genetic polymorphisms and haplotype frequencies of CYP1A2 in a Japanese population, the enhancer and promoter regions, all the exons with their surrounding introns, and intron 1 were sequenced from genomic DNA from 250 Japanese subjects. Thirty-three polymorphisms were found, including 13 novel ones: 2 in the enhancer region, 5 in the exons, and 6 in the introns. The most common single nucleotide polymorphism (SNP) was -163C>A (CYP1A2*1F allele) with a 0.628 frequency. In addition to six previously reported non-synonymous SNPs, three novel ones, 125C>G (P42R, CYP1A2*15 allele, MPJ6_1A2032), 1130G>A (R377Q, *16 allele, MPJ6_1A2033), and 1367G>A (R456H, *8 allele, MPJ6_1A2019), were found with frequencies of 0.002, 0.002, and 0.004, respectively. No polymorphism was found in the known nuclear transcriptional factor-binding sites in the enhancer region. Based on linkage disequilibrium analysis, the CYP1A2 gene was analyzed as one haplotype block. Using the 33 detected polymorphisms, 14 haplotypes were unambiguously identified, and 17 haplotypes were inferred by aid of an expectation-maximization-based program. Among them, the second major haplotype CYP1A2*1L is composed of -3860G>A (*1C allele), -2467delT (*1D allele), and -163C>A (*1F allele). Network analysis suggested that relatively rare haplotypes were derived from three major haplotypes, *1A, *1M, and *1N in most cases. Our findings provide fundamental and useful information for genotyping CYP1A2 in the Japanese, and probably Asian populations.
authors.affiliation: Project Team for Pharmacogenetics, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Soyama
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Nobumitsu
authors.initials: N
authors.lastname: Hanioka
authors.forename: Keiko
authors.initials: K
authors.lastname: Maekawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Komamura
authors.forename: Shiro
authors.initials: S
authors.lastname: Kamakura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
authors.forename: Hitonobu
authors.initials: H
authors.lastname: Tomoike
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ueno
authors.forename: Yu-ichi
authors.initials: Y
authors.lastname: Goto
authors.forename: Hideo
authors.initials: H
authors.lastname: Kimura
authors.forename: Masaaki
authors.initials: M
authors.lastname: Katoh
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugai
authors.forename: Osamu
authors.initials: O
authors.lastname: Saitoh
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kawai
authors.forename: Teiichi
authors.initials: T
authors.lastname: Ohnuma
authors.forename: Taisuke
authors.initials: T
authors.lastname: Ohtsuki
authors.forename: Chieko
authors.initials: C
authors.lastname: Suzuki
authors.forename: Narihiro
authors.initials: N
authors.lastname: Minami
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Shogo
authors.initials: S
authors.lastname: Ozawa
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Sawada
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D000927:Anticonvulsants / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D001483:Base Sequence; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D004742:Enhancer Elements, Genetic; D004827:Epilepsy / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D007564:Japan; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D000927:Anticonvulsants; D017931:DNA Primers; D004247:DNA; D019388:Cytochrome P-450 CYP1A2