The implication of the polymorphisms of COX-1, UGT1A6, and CYP2C9 among cardiovascular disease patients treated with aspirin

Nur Jalinna Abdul Jalil, Zakaria Bannur, A. Derahman, Oteh Maskon, Noor Darinah, Hamat Hamidi, Osama Ali, Gunasekaran, Mohd Rafizi, Nur Izatul Azreen, Teh Lay Kek, Mohd Zaki Salleh

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose. Enzymes potentially responsible for the pharmacokinetic variations of aspirin include cyclooxygenase-1 (COX-1), UDP-glucuronosyltransferase (UGT1A6) and P450 (CYP) (CYP2C9). We therefore aimed to determine the types and frequencies of variants of COX-1 (A-842G), UGT1A6 (UGT1A6*2; A541G and UGT1A6*3; A522C) and CYP2C9 (CYP2C9*3; A1075C) in the three major ethnic groups in Malaysia. In addition, the role of these polymorphisms on aspirin-induced gastritis among the patients was investigated. Methods: A total of 165 patients with cardiovascular disease who were treated with 75-150 mg daily dose of aspirin and 300 healthy volunteers were recruited. DNA was extracted from the blood samples and genotyped for COX-1 (A-842G), UGT1A6 (UGT1A6*2 and UGT1A6*3) and CYP2C9 (CYP2C9*3; A1075C) using allele specific polymerase chain reaction (AS-PCR). Results: Variants UGT1A6*2, *3 and CYP2C9*3 were detected in relatively high percentage of 22.83%, 30.0% and 6.50%, respectively; while COX-1 (A-842G) was absent. The genotype frequencies for UGT1A6*2 and *3 were significantly different between Indians and Malays or Chinese. The level of bilirubin among patients with different genotypes of UGT1A6 was significantly different (p-value <0.05). In addition, CYP2C9*3 was found to be associated with gastritis with an odd ratio of 6.8 (95 % Cl OR: 1.39 - 33.19; P = 0.033). Conclusion: Screening of patients with defective genetic variants of UGT1A6 and CYP2C9*3 helps in identifying patients at risk of aspirin induced gastritis. However, a randomised clinical study of bigger sample size would be needed before it is translated to clinical use.

Original languageEnglish
Pages (from-to)474-483
Number of pages10
JournalJournal of Pharmacy and Pharmaceutical Sciences
Volume18
Issue number3
Publication statusPublished - 30 Sep 2015

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Cyclooxygenase 1
Aspirin
Cardiovascular Diseases
Gastritis
Genotype
Cytochrome P-450 CYP2C9
Malaysia
Bilirubin
Ethnic Groups
Sample Size
Healthy Volunteers
Pharmacokinetics
Alleles
Odds Ratio
Polymerase Chain Reaction
DNA
Enzymes

Keywords

  • Aspirin
  • COX-1
  • CYP2C9
  • UGT1A6

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology

Cite this

Abdul Jalil, N. J., Bannur, Z., Derahman, A., Maskon, O., Darinah, N., Hamidi, H., ... Salleh, M. Z. (2015). The implication of the polymorphisms of COX-1, UGT1A6, and CYP2C9 among cardiovascular disease patients treated with aspirin. Journal of Pharmacy and Pharmaceutical Sciences, 18(3), 474-483.

The implication of the polymorphisms of COX-1, UGT1A6, and CYP2C9 among cardiovascular disease patients treated with aspirin. / Abdul Jalil, Nur Jalinna; Bannur, Zakaria; Derahman, A.; Maskon, Oteh; Darinah, Noor; Hamidi, Hamat; Ali, Osama; Gunasekaran; Rafizi, Mohd; Azreen, Nur Izatul; Kek, Teh Lay; Salleh, Mohd Zaki.

In: Journal of Pharmacy and Pharmaceutical Sciences, Vol. 18, No. 3, 30.09.2015, p. 474-483.

Research output: Contribution to journalArticle

Abdul Jalil, NJ, Bannur, Z, Derahman, A, Maskon, O, Darinah, N, Hamidi, H, Ali, O, Gunasekaran, Rafizi, M, Azreen, NI, Kek, TL & Salleh, MZ 2015, 'The implication of the polymorphisms of COX-1, UGT1A6, and CYP2C9 among cardiovascular disease patients treated with aspirin', Journal of Pharmacy and Pharmaceutical Sciences, vol. 18, no. 3, pp. 474-483.
Abdul Jalil, Nur Jalinna ; Bannur, Zakaria ; Derahman, A. ; Maskon, Oteh ; Darinah, Noor ; Hamidi, Hamat ; Ali, Osama ; Gunasekaran ; Rafizi, Mohd ; Azreen, Nur Izatul ; Kek, Teh Lay ; Salleh, Mohd Zaki. / The implication of the polymorphisms of COX-1, UGT1A6, and CYP2C9 among cardiovascular disease patients treated with aspirin. In: Journal of Pharmacy and Pharmaceutical Sciences. 2015 ; Vol. 18, No. 3. pp. 474-483.
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abstract = "Purpose. Enzymes potentially responsible for the pharmacokinetic variations of aspirin include cyclooxygenase-1 (COX-1), UDP-glucuronosyltransferase (UGT1A6) and P450 (CYP) (CYP2C9). We therefore aimed to determine the types and frequencies of variants of COX-1 (A-842G), UGT1A6 (UGT1A6*2; A541G and UGT1A6*3; A522C) and CYP2C9 (CYP2C9*3; A1075C) in the three major ethnic groups in Malaysia. In addition, the role of these polymorphisms on aspirin-induced gastritis among the patients was investigated. Methods: A total of 165 patients with cardiovascular disease who were treated with 75-150 mg daily dose of aspirin and 300 healthy volunteers were recruited. DNA was extracted from the blood samples and genotyped for COX-1 (A-842G), UGT1A6 (UGT1A6*2 and UGT1A6*3) and CYP2C9 (CYP2C9*3; A1075C) using allele specific polymerase chain reaction (AS-PCR). Results: Variants UGT1A6*2, *3 and CYP2C9*3 were detected in relatively high percentage of 22.83{\%}, 30.0{\%} and 6.50{\%}, respectively; while COX-1 (A-842G) was absent. The genotype frequencies for UGT1A6*2 and *3 were significantly different between Indians and Malays or Chinese. The level of bilirubin among patients with different genotypes of UGT1A6 was significantly different (p-value <0.05). In addition, CYP2C9*3 was found to be associated with gastritis with an odd ratio of 6.8 (95 {\%} Cl OR: 1.39 - 33.19; P = 0.033). Conclusion: Screening of patients with defective genetic variants of UGT1A6 and CYP2C9*3 helps in identifying patients at risk of aspirin induced gastritis. However, a randomised clinical study of bigger sample size would be needed before it is translated to clinical use.",
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T1 - The implication of the polymorphisms of COX-1, UGT1A6, and CYP2C9 among cardiovascular disease patients treated with aspirin

AU - Abdul Jalil, Nur Jalinna

AU - Bannur, Zakaria

AU - Derahman, A.

AU - Maskon, Oteh

AU - Darinah, Noor

AU - Hamidi, Hamat

AU - Ali, Osama

AU - Gunasekaran,

AU - Rafizi, Mohd

AU - Azreen, Nur Izatul

AU - Kek, Teh Lay

AU - Salleh, Mohd Zaki

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N2 - Purpose. Enzymes potentially responsible for the pharmacokinetic variations of aspirin include cyclooxygenase-1 (COX-1), UDP-glucuronosyltransferase (UGT1A6) and P450 (CYP) (CYP2C9). We therefore aimed to determine the types and frequencies of variants of COX-1 (A-842G), UGT1A6 (UGT1A6*2; A541G and UGT1A6*3; A522C) and CYP2C9 (CYP2C9*3; A1075C) in the three major ethnic groups in Malaysia. In addition, the role of these polymorphisms on aspirin-induced gastritis among the patients was investigated. Methods: A total of 165 patients with cardiovascular disease who were treated with 75-150 mg daily dose of aspirin and 300 healthy volunteers were recruited. DNA was extracted from the blood samples and genotyped for COX-1 (A-842G), UGT1A6 (UGT1A6*2 and UGT1A6*3) and CYP2C9 (CYP2C9*3; A1075C) using allele specific polymerase chain reaction (AS-PCR). Results: Variants UGT1A6*2, *3 and CYP2C9*3 were detected in relatively high percentage of 22.83%, 30.0% and 6.50%, respectively; while COX-1 (A-842G) was absent. The genotype frequencies for UGT1A6*2 and *3 were significantly different between Indians and Malays or Chinese. The level of bilirubin among patients with different genotypes of UGT1A6 was significantly different (p-value <0.05). In addition, CYP2C9*3 was found to be associated with gastritis with an odd ratio of 6.8 (95 % Cl OR: 1.39 - 33.19; P = 0.033). Conclusion: Screening of patients with defective genetic variants of UGT1A6 and CYP2C9*3 helps in identifying patients at risk of aspirin induced gastritis. However, a randomised clinical study of bigger sample size would be needed before it is translated to clinical use.

AB - Purpose. Enzymes potentially responsible for the pharmacokinetic variations of aspirin include cyclooxygenase-1 (COX-1), UDP-glucuronosyltransferase (UGT1A6) and P450 (CYP) (CYP2C9). We therefore aimed to determine the types and frequencies of variants of COX-1 (A-842G), UGT1A6 (UGT1A6*2; A541G and UGT1A6*3; A522C) and CYP2C9 (CYP2C9*3; A1075C) in the three major ethnic groups in Malaysia. In addition, the role of these polymorphisms on aspirin-induced gastritis among the patients was investigated. Methods: A total of 165 patients with cardiovascular disease who were treated with 75-150 mg daily dose of aspirin and 300 healthy volunteers were recruited. DNA was extracted from the blood samples and genotyped for COX-1 (A-842G), UGT1A6 (UGT1A6*2 and UGT1A6*3) and CYP2C9 (CYP2C9*3; A1075C) using allele specific polymerase chain reaction (AS-PCR). Results: Variants UGT1A6*2, *3 and CYP2C9*3 were detected in relatively high percentage of 22.83%, 30.0% and 6.50%, respectively; while COX-1 (A-842G) was absent. The genotype frequencies for UGT1A6*2 and *3 were significantly different between Indians and Malays or Chinese. The level of bilirubin among patients with different genotypes of UGT1A6 was significantly different (p-value <0.05). In addition, CYP2C9*3 was found to be associated with gastritis with an odd ratio of 6.8 (95 % Cl OR: 1.39 - 33.19; P = 0.033). Conclusion: Screening of patients with defective genetic variants of UGT1A6 and CYP2C9*3 helps in identifying patients at risk of aspirin induced gastritis. However, a randomised clinical study of bigger sample size would be needed before it is translated to clinical use.

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