The implication of the polymorphisms of COX-1, UGT1A6, and CYP2C9 among cardiovascular disease patients treated with aspirin. The Journal of Pharmacy and Pharmaceutical Sciences (JPPS), 18 (3). pp. 474-483. ISSN 1482-1826 (2015)
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; A541Gand 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*2and 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 *3were significantly different between Indians and Malays or Chinese. The level of bilirubin among patients with different genotypes of UGT1A6was 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 UGT1A6and CYP2C9*3helps 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.
| Item Type: | Article |
|---|---|
| Keywords: | COX-1, UGT1A6, CYP2C9, Aspirin, Polymorphisms, Pharmacokinetics, Gastritis, Genotyping |
| Taxonomy: | By Niche > Genome > Human Genome By Niche > Genome > Human Genome Research |
| Local Content Hub: | Niche > Genome |
| Depositing User: | Hazrul Amir Tomyang (Puncak Alam) |
| Date Deposited: | 12 Jun 2024 09:41 |
| Last Modified: | 12 Jun 2024 09:41 |
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