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J Biochem. 1999 Apr;125(4):803-8.

Genetic polymorphism in the 5'-flanking region of human CYP1A2 gene: effect on the CYP1A2 inducibility in humans.

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  • 1Laboratory of Drug Metabolism, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, 060-0812, Japan.

Abstract

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.

PMID:
10101295
[PubMed - indexed for MEDLINE]
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