Mutational analysis of CYP2C8 in hypertensive patients using denaturing high performance liquid chromatography.

What is known and Objective: CYP2C8 is involved in the cytochrome P450 (CYP) epoxygenase pathway. Arachidonic acid metabolites such as epoxyeicosatrienenoic acids and hydroxyeicosatetrenoic acids, produced may have a role in hypertension. We aimed to develop a medium through-put method for screeni...

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Main Authors: Teh, Lay Kek, Zahri, Mohd. Khiari, Zakaria, Zainul Amiruddin, Ismail, Rusli, Salleh, Mohd. Zaki
Format: Article
Language:English
English
Published: Blackwell Publishing Ltd. 2010
Online Access:http://psasir.upm.edu.my/id/eprint/15767/1/Mutational%20analysis%20of%20CYP2C8%20in%20hypertensive%20patients%20using%20denaturing%20high%20performance%20liquid%20chromatography.pdf
http://psasir.upm.edu.my/id/eprint/15767/
http://www.wiley.com
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spelling my.upm.eprints.157672016-01-12T07:17:06Z http://psasir.upm.edu.my/id/eprint/15767/ Mutational analysis of CYP2C8 in hypertensive patients using denaturing high performance liquid chromatography. Teh, Lay Kek Zahri, Mohd. Khiari Zakaria, Zainul Amiruddin Ismail, Rusli Salleh, Mohd. Zaki What is known and Objective: CYP2C8 is involved in the cytochrome P450 (CYP) epoxygenase pathway. Arachidonic acid metabolites such as epoxyeicosatrienenoic acids and hydroxyeicosatetrenoic acids, produced may have a role in hypertension. We aimed to develop a medium through-put method for screening samples of known and new mutations of CYP2C8 using denaturing high performance liquid chromatography (DHPLC). Methods: DNA samples from 200 subjects (hypertensive patients and healthy controls) were screened for SNPs in CYP2C8 using DHPLC. Genotypes and allelic frequencies of CYP2C8 between the healthy controls and patients with hypertension were compared. Results and Discussions: Six variants were detected and two were new; T deletion at 5063 and substitution of C to T at 33468 in exon 8. Differences in variant frequencies were detected between the controls and hypertensive patients. The controls have significantly higher prevalence of C35322C compared to the patients. The functional significance of the SNP at 35322 requires further study. Having homozygous C35322C could be a protective factor for hypertension. What is new and Conclusion: Denaturing high performance liquid chromatography is useful for population screening to identify new and existing SNPs. A higher frequency of the C35322T SNP was observed among hypertensive patients than control subjects. This potentially important observation requires confirmation and the clinical significance assessed. Blackwell Publishing Ltd. 2010-12 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/15767/1/Mutational%20analysis%20of%20CYP2C8%20in%20hypertensive%20patients%20using%20denaturing%20high%20performance%20liquid%20chromatography.pdf Teh, Lay Kek and Zahri, Mohd. Khiari and Zakaria, Zainul Amiruddin and Ismail, Rusli and Salleh, Mohd. Zaki (2010) Mutational analysis of CYP2C8 in hypertensive patients using denaturing high performance liquid chromatography. Journal of Clinical Pharmacy and Therapeutics, 35 (6). pp. 723-728. ISSN 0269-4727, ESSN: 1365-2710 http://www.wiley.com 10.1111/j.1365-2710.2009.01146.x English
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
English
description What is known and Objective: CYP2C8 is involved in the cytochrome P450 (CYP) epoxygenase pathway. Arachidonic acid metabolites such as epoxyeicosatrienenoic acids and hydroxyeicosatetrenoic acids, produced may have a role in hypertension. We aimed to develop a medium through-put method for screening samples of known and new mutations of CYP2C8 using denaturing high performance liquid chromatography (DHPLC). Methods: DNA samples from 200 subjects (hypertensive patients and healthy controls) were screened for SNPs in CYP2C8 using DHPLC. Genotypes and allelic frequencies of CYP2C8 between the healthy controls and patients with hypertension were compared. Results and Discussions: Six variants were detected and two were new; T deletion at 5063 and substitution of C to T at 33468 in exon 8. Differences in variant frequencies were detected between the controls and hypertensive patients. The controls have significantly higher prevalence of C35322C compared to the patients. The functional significance of the SNP at 35322 requires further study. Having homozygous C35322C could be a protective factor for hypertension. What is new and Conclusion: Denaturing high performance liquid chromatography is useful for population screening to identify new and existing SNPs. A higher frequency of the C35322T SNP was observed among hypertensive patients than control subjects. This potentially important observation requires confirmation and the clinical significance assessed.
format Article
author Teh, Lay Kek
Zahri, Mohd. Khiari
Zakaria, Zainul Amiruddin
Ismail, Rusli
Salleh, Mohd. Zaki
spellingShingle Teh, Lay Kek
Zahri, Mohd. Khiari
Zakaria, Zainul Amiruddin
Ismail, Rusli
Salleh, Mohd. Zaki
Mutational analysis of CYP2C8 in hypertensive patients using denaturing high performance liquid chromatography.
author_facet Teh, Lay Kek
Zahri, Mohd. Khiari
Zakaria, Zainul Amiruddin
Ismail, Rusli
Salleh, Mohd. Zaki
author_sort Teh, Lay Kek
title Mutational analysis of CYP2C8 in hypertensive patients using denaturing high performance liquid chromatography.
title_short Mutational analysis of CYP2C8 in hypertensive patients using denaturing high performance liquid chromatography.
title_full Mutational analysis of CYP2C8 in hypertensive patients using denaturing high performance liquid chromatography.
title_fullStr Mutational analysis of CYP2C8 in hypertensive patients using denaturing high performance liquid chromatography.
title_full_unstemmed Mutational analysis of CYP2C8 in hypertensive patients using denaturing high performance liquid chromatography.
title_sort mutational analysis of cyp2c8 in hypertensive patients using denaturing high performance liquid chromatography.
publisher Blackwell Publishing Ltd.
publishDate 2010
url http://psasir.upm.edu.my/id/eprint/15767/1/Mutational%20analysis%20of%20CYP2C8%20in%20hypertensive%20patients%20using%20denaturing%20high%20performance%20liquid%20chromatography.pdf
http://psasir.upm.edu.my/id/eprint/15767/
http://www.wiley.com
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score 13.211869