TY - JOUR
T1 - Genetic polymorphism in the 5'-flanking region of human CYP1A2 gene
T2 - Effect on the CYP1A2 inducibility in humans
AU - Nakajima, Miki
AU - Yokoi, Tsuyoshi
AU - Mizutani, Mayumi
AU - Kinoshita, Moritoshi
AU - Funayama, Masato
AU - Kamataki, Tetsuya
PY - 1999
Y1 - 1999
N2 - A genetic polymorphism was identified in the 5'-flanking region of human CYP1A2 gene, and its effect on the transcriptional activation of the CYP1A2 gene was investigated. Nucleotide sequence analysis revealed the existence of a point mutation from guanine (wild type) to adenine (mutated type) at position -2964 in the gene. This point mutation was detected by a polymerase chain reaction-restriction fragment length polymorphism method using DdeI or BslI restriction enzyme, and was proven to be genetically inherited. Allele frequency in 116 Japanese subjects showed 0.77 and 0.23 for the wild and mutated types of allele, respectively. The point mutation caused a significant decrease of CYP1A2 activity measured by the rate of caffeine 3-demethylation in Japanese smokers (p < 0.05). Gel retardation analysis showed the existence of protein bound to the polymorphic locus. These results suggest that this polymorphism is a causal factor of decreased CYP1A2 inducibility.
AB - A genetic polymorphism was identified in the 5'-flanking region of human CYP1A2 gene, and its effect on the transcriptional activation of the CYP1A2 gene was investigated. Nucleotide sequence analysis revealed the existence of a point mutation from guanine (wild type) to adenine (mutated type) at position -2964 in the gene. This point mutation was detected by a polymerase chain reaction-restriction fragment length polymorphism method using DdeI or BslI restriction enzyme, and was proven to be genetically inherited. Allele frequency in 116 Japanese subjects showed 0.77 and 0.23 for the wild and mutated types of allele, respectively. The point mutation caused a significant decrease of CYP1A2 activity measured by the rate of caffeine 3-demethylation in Japanese smokers (p < 0.05). Gel retardation analysis showed the existence of protein bound to the polymorphic locus. These results suggest that this polymorphism is a causal factor of decreased CYP1A2 inducibility.
KW - Caffeine metabolism
KW - Cigarette smoking
KW - Induction
KW - PCR-RFLP
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U2 - 10.1093/oxfordjournals.jbchem.a022352
DO - 10.1093/oxfordjournals.jbchem.a022352
M3 - Article
C2 - 10101295
AN - SCOPUS:0032929010
VL - 125
SP - 803
EP - 808
JO - Journal of Biochemistry
JF - Journal of Biochemistry
SN - 0021-924X
IS - 4
ER -