title: The Implication of the Polymorphisms of COX-1, UGT1A6, and CYP2C9 among Cardiovascular Disease (CVD) Patients Treated with Aspirin.
abstract: OBJECTIVE
  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 &lt; 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA, Selangor, Malaysia.
authors.forename: Nur Jalinna Abdul
authors.initials: NJ
authors.lastname: Jalil
authors.forename: Zakaria
authors.initials: Z
authors.lastname: Bannur
authors.forename: A
authors.initials: A
authors.lastname: Derahman
authors.forename: O
authors.initials: O
authors.lastname: Maskon
authors.forename: Noor
authors.initials: N
authors.lastname: Darinah
authors.forename: Hamat
authors.initials: H
authors.lastname: Hamidi
authors.forename: Osama Ali
authors.initials: OA
authors.lastname: Gunasekaran
authors.forename: Mohd
authors.initials: M
authors.lastname: Rafizi
authors.forename: Nur Izatul
authors.initials: NI
authors.lastname: Azreen
authors.forename: Teh Lay
authors.initials: TL
authors.lastname: Kek
authors.forename: Mohd Zaki
authors.initials: MZ
authors.lastname: Salleh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000235:genetics*; D051545:Cyclooxygenase 1 / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D005260:Female; D005756:Gastritis / Q000139:chemically induced / Q000235:genetics; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D016896:Treatment Outcome; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase; D001241:Aspirin