Structural characterization of a new variant of the CYP2A6 gene (CYP2A6*1B) apparently diagnosed as heterozygotes of CYP2A6*1A and CYP2A6*4C

Noritaka Ariyoshi, Y. Takahashi, M. Miyamoto, Y. Umetsu, S. Daigo, T. Tateishi, S. I. Kobayashi, Y. Mizorogi, M. A. Loriot, I. Stucker, P. Beaune, M. Kinoshita, T. Kamataki

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

During the course of investigating the frequency of a CYP2A6 whole deletion-type polymorphism (CYP2A6*4C) in Japanese, an unexpectedly large population of heterozygotes for CYP2A6*4C and the wild-type (CYP2A6*1A) was found. Cloning of a cDNA encoding CYP2A6 from the liver of individuals judged as heterozygotes for CYP2A6*4C and the CYP2A6*1A was carried out to identify the causal allele(s) responsible for a possible overestimation. A clone isolated from the liver cDNA library possessed 58 bp sequences in the 3'-untranslated region, which was replaced with the corresponding region of the CYP2A7 gene. The same gene conversion existed in the genomic DNA, indicating that the replacement was not a cloning artifact. Based on the gene structure of the allele (CYP2A6*1B), this variant was thought to be one of the causal alleles responsible for overestimation of heterozygotes for CYP2A6*4C and CYP2A6*1A. To investigate this further, we developed a genotyping method which could distinguish the CYP2A6*1A, CYP2A6*1B and CYP2A6*4C alleles from each other. The results clearly showed that CYP2A6*1B was the sole allele responsible for the overestimation. We conclude that the new genotyping method allows determination of six genotypes of the CYP2A6 gene, simultaneously and precisely, in both Oriental and Caucasian populations. (C) 2000 Lippincott Williams and Wilkins.

Original languageEnglish
Pages (from-to)687-693
Number of pages7
JournalPharmacogenetics
Volume10
Issue number8
DOIs
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Heterozygote
Alleles
Genes
Organism Cloning
Gene Conversion
Liver
3' Untranslated Regions
Gene Library
Artifacts
Population
Complementary DNA
Clone Cells
Genotype
DNA

Keywords

  • 3'-Untranslated region
  • Cytochrome P450
  • Genetic polymorphism
  • Genotyping

ASJC Scopus subject areas

  • Genetics
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Structural characterization of a new variant of the CYP2A6 gene (CYP2A6*1B) apparently diagnosed as heterozygotes of CYP2A6*1A and CYP2A6*4C. / Ariyoshi, Noritaka; Takahashi, Y.; Miyamoto, M.; Umetsu, Y.; Daigo, S.; Tateishi, T.; Kobayashi, S. I.; Mizorogi, Y.; Loriot, M. A.; Stucker, I.; Beaune, P.; Kinoshita, M.; Kamataki, T.

In: Pharmacogenetics, Vol. 10, No. 8, 2000, p. 687-693.

Research output: Contribution to journalArticle

Ariyoshi, N, Takahashi, Y, Miyamoto, M, Umetsu, Y, Daigo, S, Tateishi, T, Kobayashi, SI, Mizorogi, Y, Loriot, MA, Stucker, I, Beaune, P, Kinoshita, M & Kamataki, T 2000, 'Structural characterization of a new variant of the CYP2A6 gene (CYP2A6*1B) apparently diagnosed as heterozygotes of CYP2A6*1A and CYP2A6*4C', Pharmacogenetics, vol. 10, no. 8, pp. 687-693. https://doi.org/10.1097/00008571-200011000-00003
Ariyoshi, Noritaka ; Takahashi, Y. ; Miyamoto, M. ; Umetsu, Y. ; Daigo, S. ; Tateishi, T. ; Kobayashi, S. I. ; Mizorogi, Y. ; Loriot, M. A. ; Stucker, I. ; Beaune, P. ; Kinoshita, M. ; Kamataki, T. / Structural characterization of a new variant of the CYP2A6 gene (CYP2A6*1B) apparently diagnosed as heterozygotes of CYP2A6*1A and CYP2A6*4C. In: Pharmacogenetics. 2000 ; Vol. 10, No. 8. pp. 687-693.
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abstract = "During the course of investigating the frequency of a CYP2A6 whole deletion-type polymorphism (CYP2A6*4C) in Japanese, an unexpectedly large population of heterozygotes for CYP2A6*4C and the wild-type (CYP2A6*1A) was found. Cloning of a cDNA encoding CYP2A6 from the liver of individuals judged as heterozygotes for CYP2A6*4C and the CYP2A6*1A was carried out to identify the causal allele(s) responsible for a possible overestimation. A clone isolated from the liver cDNA library possessed 58 bp sequences in the 3'-untranslated region, which was replaced with the corresponding region of the CYP2A7 gene. The same gene conversion existed in the genomic DNA, indicating that the replacement was not a cloning artifact. Based on the gene structure of the allele (CYP2A6*1B), this variant was thought to be one of the causal alleles responsible for overestimation of heterozygotes for CYP2A6*4C and CYP2A6*1A. To investigate this further, we developed a genotyping method which could distinguish the CYP2A6*1A, CYP2A6*1B and CYP2A6*4C alleles from each other. The results clearly showed that CYP2A6*1B was the sole allele responsible for the overestimation. We conclude that the new genotyping method allows determination of six genotypes of the CYP2A6 gene, simultaneously and precisely, in both Oriental and Caucasian populations. (C) 2000 Lippincott Williams and Wilkins.",
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T1 - Structural characterization of a new variant of the CYP2A6 gene (CYP2A6*1B) apparently diagnosed as heterozygotes of CYP2A6*1A and CYP2A6*4C

AU - Ariyoshi, Noritaka

AU - Takahashi, Y.

AU - Miyamoto, M.

AU - Umetsu, Y.

AU - Daigo, S.

AU - Tateishi, T.

AU - Kobayashi, S. I.

AU - Mizorogi, Y.

AU - Loriot, M. A.

AU - Stucker, I.

AU - Beaune, P.

AU - Kinoshita, M.

AU - Kamataki, T.

PY - 2000

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N2 - During the course of investigating the frequency of a CYP2A6 whole deletion-type polymorphism (CYP2A6*4C) in Japanese, an unexpectedly large population of heterozygotes for CYP2A6*4C and the wild-type (CYP2A6*1A) was found. Cloning of a cDNA encoding CYP2A6 from the liver of individuals judged as heterozygotes for CYP2A6*4C and the CYP2A6*1A was carried out to identify the causal allele(s) responsible for a possible overestimation. A clone isolated from the liver cDNA library possessed 58 bp sequences in the 3'-untranslated region, which was replaced with the corresponding region of the CYP2A7 gene. The same gene conversion existed in the genomic DNA, indicating that the replacement was not a cloning artifact. Based on the gene structure of the allele (CYP2A6*1B), this variant was thought to be one of the causal alleles responsible for overestimation of heterozygotes for CYP2A6*4C and CYP2A6*1A. To investigate this further, we developed a genotyping method which could distinguish the CYP2A6*1A, CYP2A6*1B and CYP2A6*4C alleles from each other. The results clearly showed that CYP2A6*1B was the sole allele responsible for the overestimation. We conclude that the new genotyping method allows determination of six genotypes of the CYP2A6 gene, simultaneously and precisely, in both Oriental and Caucasian populations. (C) 2000 Lippincott Williams and Wilkins.

AB - During the course of investigating the frequency of a CYP2A6 whole deletion-type polymorphism (CYP2A6*4C) in Japanese, an unexpectedly large population of heterozygotes for CYP2A6*4C and the wild-type (CYP2A6*1A) was found. Cloning of a cDNA encoding CYP2A6 from the liver of individuals judged as heterozygotes for CYP2A6*4C and the CYP2A6*1A was carried out to identify the causal allele(s) responsible for a possible overestimation. A clone isolated from the liver cDNA library possessed 58 bp sequences in the 3'-untranslated region, which was replaced with the corresponding region of the CYP2A7 gene. The same gene conversion existed in the genomic DNA, indicating that the replacement was not a cloning artifact. Based on the gene structure of the allele (CYP2A6*1B), this variant was thought to be one of the causal alleles responsible for overestimation of heterozygotes for CYP2A6*4C and CYP2A6*1A. To investigate this further, we developed a genotyping method which could distinguish the CYP2A6*1A, CYP2A6*1B and CYP2A6*4C alleles from each other. The results clearly showed that CYP2A6*1B was the sole allele responsible for the overestimation. We conclude that the new genotyping method allows determination of six genotypes of the CYP2A6 gene, simultaneously and precisely, in both Oriental and Caucasian populations. (C) 2000 Lippincott Williams and Wilkins.

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