Efficient screening method of the thiopurine methyltransferase polymorphisms for patients considering taking thiopurine drugs in a Chinese Han population in Henan Province (central China)
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| Title: | Efficient screening method of the thiopurine methyltransferase polymorphisms for patients considering taking thiopurine drugs in a Chinese Han population in Henan Province (central China) |
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| Authors: | Zhang, Li-Rong1 lrzhang@zzu.edu.cn, Song, Dong-Kui2, Zhang, Wei2, Zhao, Jun1, Jia, Lin-jing1, Xing, Dong-Liang2 |
| Source: | Clinica Chimica Acta. Feb2007, Vol. 376 Issue 1/2, p45-51. 7p. |
| Subjects: | Genetic polymorphisms, Population genetics, Fibrinogen polymorphisms, Drugs |
| Abstract: | Abstract: Background: Thiopurine S-methyltransferase (TPMT) is an enzyme that catalyzed the S-methylation of thiopurine drugs. TPMT activity exhibits an interindividual variability, mainly as a result of genetic polymorphism. Patients with intermediate or deficient TPMT activity are at risk for toxicity after receiving standard doses of thiopurine drugs. We determined a cut-off concentration of the TPMT activity assay less than which genotyping of the TPMT gene should be performed. In addition, the influence of hemodialysis on TPMT activity in uremic patients was examined. Methods: In 248 healthy subjects and 30 uremic patients, PCR-based methods were used to analyze the most common functional mutations TPMT⁎2, ⁎3A, ⁎3B and ⁎3C. A HPLC assay was used to measure erythrocyte TPMT activity in the whole population. Results: Seven TPMT⁎3C heterozygotes were identified, while TPMT⁎2, ⁎3A and ⁎3B alleles were not detected in 248 healthy subjects. The frequency of TPMT⁎3C allele was 1.4% (7/496). The TPMT activity in healthy subjects was normally distributed, ranged from 6.09 to 28.65 nmol/h/ml pRBC with a mean of 16.03±4.16 nmol/h/ml pRBC. The cut-off for high TPMT activity and intermediate TPMT activity was 10.07 nmol/h/ml pRBC. There were 19 intermediate activity healthy subjects (7.7%) and 229 high activity healthy subjects (92.3%), and no TPMT deficiency subject was found. All of the 229 healthy subjects with high activity had no mutant alleles, while 7 of the 19 subjects with intermediate activity had a mutant allele. Phenotypes were in good agreement with genotypes for 95% of subjects. The uremic patients were all homozygous for the wild-type allele whose TPMT activity was activated significantly before hemodialysis compared with TPMT activity after hemodialysis. Conclusions: We defined the cut-off values for the TPMT phenotyping assay at 10.07 nmol/h/ml pRBC, less than which additional genotyping elucidates the individual risk for drug therapy. In uremic patients, TPMT activity is increased by some uremic factors, and dialysis shifted their TPMT activity close to that of a healthy control group. [Copyright &y& Elsevier] |
| Copyright of Clinica Chimica Acta is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 23448762 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Efficient screening method of the thiopurine methyltransferase polymorphisms for patients considering taking thiopurine drugs in a Chinese Han population in Henan Province (central China) – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Zhang%2C+Li-Rong%22">Zhang, Li-Rong</searchLink><relatesTo>1</relatesTo><i> lrzhang@zzu.edu.cn</i><br /><searchLink fieldCode="AR" term="%22Song%2C+Dong-Kui%22">Song, Dong-Kui</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Zhang%2C+Wei%22">Zhang, Wei</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Zhao%2C+Jun%22">Zhao, Jun</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Jia%2C+Lin-jing%22">Jia, Lin-jing</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Xing%2C+Dong-Liang%22">Xing, Dong-Liang</searchLink><relatesTo>2</relatesTo> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Clinica+Chimica+Acta%22">Clinica Chimica Acta</searchLink>. Feb2007, Vol. 376 Issue 1/2, p45-51. 7p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Genetic+polymorphisms%22">Genetic polymorphisms</searchLink><br /><searchLink fieldCode="DE" term="%22Population+genetics%22">Population genetics</searchLink><br /><searchLink fieldCode="DE" term="%22Fibrinogen+polymorphisms%22">Fibrinogen polymorphisms</searchLink><br /><searchLink fieldCode="DE" term="%22Drugs%22">Drugs</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Abstract: Background: Thiopurine S-methyltransferase (TPMT) is an enzyme that catalyzed the S-methylation of thiopurine drugs. TPMT activity exhibits an interindividual variability, mainly as a result of genetic polymorphism. Patients with intermediate or deficient TPMT activity are at risk for toxicity after receiving standard doses of thiopurine drugs. We determined a cut-off concentration of the TPMT activity assay less than which genotyping of the TPMT gene should be performed. In addition, the influence of hemodialysis on TPMT activity in uremic patients was examined. Methods: In 248 healthy subjects and 30 uremic patients, PCR-based methods were used to analyze the most common functional mutations TPMT⁎2, ⁎3A, ⁎3B and ⁎3C. A HPLC assay was used to measure erythrocyte TPMT activity in the whole population. Results: Seven TPMT⁎3C heterozygotes were identified, while TPMT⁎2, ⁎3A and ⁎3B alleles were not detected in 248 healthy subjects. The frequency of TPMT⁎3C allele was 1.4% (7/496). The TPMT activity in healthy subjects was normally distributed, ranged from 6.09 to 28.65 nmol/h/ml pRBC with a mean of 16.03±4.16 nmol/h/ml pRBC. The cut-off for high TPMT activity and intermediate TPMT activity was 10.07 nmol/h/ml pRBC. There were 19 intermediate activity healthy subjects (7.7%) and 229 high activity healthy subjects (92.3%), and no TPMT deficiency subject was found. All of the 229 healthy subjects with high activity had no mutant alleles, while 7 of the 19 subjects with intermediate activity had a mutant allele. Phenotypes were in good agreement with genotypes for 95% of subjects. The uremic patients were all homozygous for the wild-type allele whose TPMT activity was activated significantly before hemodialysis compared with TPMT activity after hemodialysis. Conclusions: We defined the cut-off values for the TPMT phenotyping assay at 10.07 nmol/h/ml pRBC, less than which additional genotyping elucidates the individual risk for drug therapy. In uremic patients, TPMT activity is increased by some uremic factors, and dialysis shifted their TPMT activity close to that of a healthy control group. [Copyright &y& Elsevier] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Clinica Chimica Acta is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/j.cca.2006.07.010 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 7 StartPage: 45 Subjects: – SubjectFull: Genetic polymorphisms Type: general – SubjectFull: Population genetics Type: general – SubjectFull: Fibrinogen polymorphisms Type: general – SubjectFull: Drugs Type: general Titles: – TitleFull: Efficient screening method of the thiopurine methyltransferase polymorphisms for patients considering taking thiopurine drugs in a Chinese Han population in Henan Province (central China) Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Zhang, Li-Rong – PersonEntity: Name: NameFull: Song, Dong-Kui – PersonEntity: Name: NameFull: Zhang, Wei – PersonEntity: Name: NameFull: Zhao, Jun – PersonEntity: Name: NameFull: Jia, Lin-jing – PersonEntity: Name: NameFull: Xing, Dong-Liang IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 02 Text: Feb2007 Type: published Y: 2007 Identifiers: – Type: issn-print Value: 00098981 Numbering: – Type: volume Value: 376 – Type: issue Value: 1/2 Titles: – TitleFull: Clinica Chimica Acta Type: main |
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