Genetic variations of VDR/NR1I1 encoding vitamin D receptor in a Japanese population.
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.
Ukaji
Maho
M
Project Team for Pharmacogenetics, National Institute of Health Sciences, Tokyo, Japan.
Saito
Yoshiro
Y
Fukushima-Uesaka
Hiromi
H
Maekawa
Keiko
K
Katori
Noriko
N
Kaniwa
Nahoko
N
Yoshida
Teruhiko
T
Nokihara
Hiroshi
H
Sekine
Ikuo
I
Kunitoh
Hideo
H
Ohe
Yuichiro
Y
Yamamoto
Noboru
N
Tamura
Tomohide
T
Saijo
Nagahiro
N
Sawada
Jun-ichi
J
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*
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D004364:Pharmaceutical Preparations; D018167:Receptors, Calcitriol