Functional characterization of genetic polymorphisms identified in the promoter region of the xanthine oxidase gene

Mutsumi Kudo; Takamitsu Sasaki; Masaaki Ishikawa; Noriyasu Hirasawa; Masahiro Hiratsuka

doi:10.2133/dmpk.DMPK-10-NT-054

Functional characterization of genetic polymorphisms identified in the promoter region of the xanthine oxidase gene

Mutsumi Kudo, Takamitsu Sasaki, Masaaki Ishikawa, Noriyasu Hirasawa, Masahiro Hiratsuka

PHA - Pharmacy

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

Xanthine oxidase (XO) catalyzes the oxidation of endogenous and exogenous purines and pyrimidines. In the present study, we investigated polymorphisms in the promoter region of the XO gene. Sequence variations in the 5?-flanking region were screened using denaturing high-performance liquid chromatography (DHPLC) on DNA samples from 196 unrelated Japanese individuals. Thirteen polymorphisms were identified and 13 haplotypes were classified by haplotype analysis. The promoter activities of these polymorphisms were measured by luciferase assay in the human hepatoma cell lines HepG2 and Huh-7. Transcriptional activity was significantly lower in cell lines transfected with the reporter construct containing 5-kb upstream fragments with -1756T than in those with wild-type -1756C. Our results indicate that genetic variation in the promoter region of XO may determine interindividual differences in XO gene expression.

Original language	English
Pages (from-to)	599-604
Number of pages	6
Journal	Drug metabolism and pharmacokinetics
Volume	25
Issue number	6
DOIs	https://doi.org/10.2133/dmpk.DMPK-10-NT-054
Publication status	Published - 2010

Keywords

Genetic polymorphism
Promoter region
Regulation
Xanthine oxidase

ASJC Scopus subject areas

Pharmacology
Pharmaceutical Science
Pharmacology (medical)

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10.2133/dmpk.DMPK-10-NT-054

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title = "Functional characterization of genetic polymorphisms identified in the promoter region of the xanthine oxidase gene",

abstract = "Xanthine oxidase (XO) catalyzes the oxidation of endogenous and exogenous purines and pyrimidines. In the present study, we investigated polymorphisms in the promoter region of the XO gene. Sequence variations in the 5?-flanking region were screened using denaturing high-performance liquid chromatography (DHPLC) on DNA samples from 196 unrelated Japanese individuals. Thirteen polymorphisms were identified and 13 haplotypes were classified by haplotype analysis. The promoter activities of these polymorphisms were measured by luciferase assay in the human hepatoma cell lines HepG2 and Huh-7. Transcriptional activity was significantly lower in cell lines transfected with the reporter construct containing 5-kb upstream fragments with -1756T than in those with wild-type -1756C. Our results indicate that genetic variation in the promoter region of XO may determine interindividual differences in XO gene expression.",

keywords = "Genetic polymorphism, Promoter region, Regulation, Xanthine oxidase",

author = "Mutsumi Kudo and Takamitsu Sasaki and Masaaki Ishikawa and Noriyasu Hirasawa and Masahiro Hiratsuka",

note = "Funding Information: Received; June 17, 2010, Accepted; August 2, 2010, J-STAGE Advance Published Date; October 1, 2010 *To whom correspondence should be addressed: Masahiro HIRATSUKA, Ph.D., Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan. Tel & Fax. ＋81-22-717-7049, E-mail: mhira＠m.tohoku.ac.jp This work was supported by KAKENHI (20590154) from the Japan Society for the Promotion of Science (JSPS), in part by a grant from the Smoking Research Foundation and a grant from the Japan Research Foundation for Clinical Pharmacology.",

year = "2010",

doi = "10.2133/dmpk.DMPK-10-NT-054",

language = "English",

volume = "25",

pages = "599--604",

journal = "Drug Metabolism and Pharmacokinetics",

issn = "1347-4367",

publisher = "Japanese Society for the Study of Xenobiotics",

number = "6",

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T1 - Functional characterization of genetic polymorphisms identified in the promoter region of the xanthine oxidase gene

AU - Kudo, Mutsumi

AU - Sasaki, Takamitsu

AU - Ishikawa, Masaaki

AU - Hirasawa, Noriyasu

AU - Hiratsuka, Masahiro

N1 - Funding Information: Received; June 17, 2010, Accepted; August 2, 2010, J-STAGE Advance Published Date; October 1, 2010 *To whom correspondence should be addressed: Masahiro HIRATSUKA, Ph.D., Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan. Tel & Fax. ＋81-22-717-7049, E-mail: mhira＠m.tohoku.ac.jp This work was supported by KAKENHI (20590154) from the Japan Society for the Promotion of Science (JSPS), in part by a grant from the Smoking Research Foundation and a grant from the Japan Research Foundation for Clinical Pharmacology.

PY - 2010

Y1 - 2010

N2 - Xanthine oxidase (XO) catalyzes the oxidation of endogenous and exogenous purines and pyrimidines. In the present study, we investigated polymorphisms in the promoter region of the XO gene. Sequence variations in the 5?-flanking region were screened using denaturing high-performance liquid chromatography (DHPLC) on DNA samples from 196 unrelated Japanese individuals. Thirteen polymorphisms were identified and 13 haplotypes were classified by haplotype analysis. The promoter activities of these polymorphisms were measured by luciferase assay in the human hepatoma cell lines HepG2 and Huh-7. Transcriptional activity was significantly lower in cell lines transfected with the reporter construct containing 5-kb upstream fragments with -1756T than in those with wild-type -1756C. Our results indicate that genetic variation in the promoter region of XO may determine interindividual differences in XO gene expression.

AB - Xanthine oxidase (XO) catalyzes the oxidation of endogenous and exogenous purines and pyrimidines. In the present study, we investigated polymorphisms in the promoter region of the XO gene. Sequence variations in the 5?-flanking region were screened using denaturing high-performance liquid chromatography (DHPLC) on DNA samples from 196 unrelated Japanese individuals. Thirteen polymorphisms were identified and 13 haplotypes were classified by haplotype analysis. The promoter activities of these polymorphisms were measured by luciferase assay in the human hepatoma cell lines HepG2 and Huh-7. Transcriptional activity was significantly lower in cell lines transfected with the reporter construct containing 5-kb upstream fragments with -1756T than in those with wild-type -1756C. Our results indicate that genetic variation in the promoter region of XO may determine interindividual differences in XO gene expression.

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KW - Regulation

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Functional characterization of genetic polymorphisms identified in the promoter region of the xanthine oxidase gene

Abstract

Keywords

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