The Implication of the Polymorphisms of COX-1, UGT1A6, and CYP2C9 among Cardiovascular Disease (CVD) Patients Treated with Aspirin

Nur Jalinna Abdul Jalil, Zakaria Bannur, A. Derahman, O. Maskon, Noor Darinah, Hamat Hamidi, Osama Ali Gunasekaran, Mohd Rafizi, Nur Izatul Azreen, Teh Lay Kek, Mohd. Zaki Salleh
2015 Journal of Pharmacy & Pharmaceutical Sciences  
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
more » ... ients 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.
doi:10.18433/j3fc7f fatcat:b5gyxrccbvdw3il3xnqpkywr7i