title: Genetic polymorphisms and haplotype structures of the CYP4A22 gene in a Japanese population.
abstract: The CYP4A fatty acid monooxygenases oxidize endogenous arachidonic acid to 20-hydroxyeicosatetraenoic acid that acts as a regulator of blood pressure. Among the isoforms of the CYP4A subfamily, the human CYP4A22 was recently identified. In this study, we report the comprehensive investigation of polymorphisms in the CYP4A22 gene. To investigate genetic variation in CYP4A22 in 191 Japanese subjects, we used denaturing HPLC (DHPLC) and direct sequencing. Our investigation has enabled the identification of 13 sequence variations in the CYP4A22 coding region, thereby demonstrating for the first time that this gene is subject to polymorphism. Two of these sequence variations correspond to silent mutations located in exons 8 (His323His) and 9 (Gly390Gly). Nine of these sequence variations correspond to missense mutations located in exons 1 (Arg11Cys), 3 (Arg126Trp), 4 (Gly130Ser and Asn152Tyr), 5 (Val185Phe), 6 (Cys231Arg), 7 (Lys276Thr), 10 (Leu428Pro), and 12 (Leu509Phe). One of these sequence variations corresponds to nonsense mutations located in exon 9 (Gln368stop). The 13th mutation corresponds to a nucleotide deletion (G7067del) that causes a frameshift and consequently results in a stop codon 80 nucleotides downstream. In addition to the wild-type CYP4A22*1 allele, 20 variants, namely CYP4A22*2-15, were characterized by haplotype analysis. Based on these data, we concluded that allelic variants of the human CYP4A22 gene exist and speculated that some of these variants may be functionally relevant.
authors.affiliation: Department of Clinical Pharmaceutics, Tohoku Pharmaceutical University, 4-4-1, Komatsushima, Sendai 981-8558, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiratsuka
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Nozawa
authors.forename: Yuya
authors.initials: Y
authors.lastname: Katsumoto
authors.forename: Toshiko
authors.initials: T
authors.lastname: Moteki
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Sasaki
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Konno
authors.forename: Michinao
authors.initials: M
authors.lastname: Mizugaki
mesh_terms: D000483:Alleles; D001483:Base Sequence; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide
chemical_list: D017931:DNA Primers; D003577:Cytochrome P-450 Enzyme System; C471051:CYP4A22 protein, human; D042926:Cytochrome P-450 CYP4A