title: Genetic variations of VDR/NR1I1 encoding vitamin D receptor in a Japanese population.
abstract: The vitamin D receptor (VDR) is a transcriptional factor responsive to 1alpha,25-dihydroxyvitamin D(3) and lithocholic acid, and induces expression of drug metabolizing enzymes CYP3A4, CYP2B6 and CYP2C9. In this study, the promoter regions, 14 exons (including 6 exon 1's) and their flanking introns of VDR were comprehensively screened for genetic variations in 107 Japanese subjects. Sixty-one genetic variations including 25 novel ones were found: 9 in the 5'-flanking region, 2 in the 5'-untranslated region (UTR), 7 in the coding exons (5 synonymous and 2 nonsynonymous variations), 12 in the 3'-UTR, 19 in the introns between the exon 1's, and 12 in introns 2 to 8. Of these, one novel nonsynonymous variation, 154A>G (Met52Val), was detected with an allele frequency of 0.005. The single nucleotide polymorphisms (SNPs) that increase VDR expression or activity, -29649G>A, 2T>C and 1592((*)308)C>A tagging linked variations in the 3'-UTR, were detected at 0.430, 0.636, and 0.318 allele frequencies, respectively. Another SNP, -26930A>G, with reduced VDR transcription was found at a 0.028 frequency. These findings would be useful for association studies on VDR variations in Japanese.
authors.affiliation: Project Team for Pharmacogenetics, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Ukaji
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Hiromi
authors.initials: H
authors.lastname: Fukushima-Uesaka
authors.forename: Keiko
authors.initials: K
authors.lastname: Maekawa
authors.forename: Noriko
authors.initials: N
authors.lastname: Katori
authors.forename: Nahoko
authors.initials: N
authors.lastname: Kaniwa
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nokihara
authors.forename: Ikuo
authors.initials: I
authors.lastname: Sekine
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunitoh
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Saijo
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Sawada
mesh_terms: D020413:3' Untranslated Regions; D024506:5' Flanking Region; D020121:5' Untranslated Regions; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007438:Introns; D007564:Japan; D008969:Molecular Sequence Data; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D004364:Pharmaceutical Preparations; D018167:Receptors, Calcitriol