Polymorphisms in genes encoding acetylsalicylic acid metabolizing enzymes are unrelated to upper gastrointestinal health in cardiovascular patients on acetylsalicylic acid

Br J Clin Pharmacol. 2005 Dec;60(6):623-8. doi: 10.1111/j.1365-2125.2005.02495.x.

Abstract

Background: As acetylsalicylic acid is metabolized by UDP-glucuronosyltransferase 1A6 (UGT1A6) and cytochrome P450 2C9 (CYP2C9), interindividual differences in activity of these enzymes may modulate the effects and side-effects of acetylsalicylic acid. The objective of this study was to assess whether polymorphisms in UGT1A6 and CYP2C9 genes are related to the prevalence of upper gastrointestinal symptoms in cardiovascular patients using acetylsalicylic acid for secondary prevention of ischaemic heart disease.

Methods: Blood samples were taken from acetylsalicylic acid using patients admitted to the Coronary Care Unit. Dyspepsia-related health was evaluated at week 2, using a validated upper gastrointestinal complaint questionnaire. A subset of 160 patients responded to a survey and were eligible to participate in this study. DNA was isolated and UGT1A6 and CYP2C9 genotypes were determined using polymerase chain reaction restricted fragment length polymorphism techniques.

Results: Seventy per cent of the patients returned the questionnaire. UGT1A6 and CYP2C9 variant polymorphisms were found in 103 (63%) and 56 (35%) patients, respectively. There was no association between gastrointestinal symptoms and UGT1A6 (OR = 0.80, 95% CI = 0.41-1.56) or CYP2C9 polymorphisms (OR = 0.85, 95% CI = 0.44-1.67).

Conclusions: There was no association between polymorphisms in genes encoding for acetylsalicylic acid metabolizing enzymes on the prevalence of gastric complaints in cardiovascular patients on acetylsalicylic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Aspirin / adverse effects*
  • Aspirin / pharmacokinetics
  • Aspirin / therapeutic use
  • Cardiovascular Diseases / prevention & control*
  • Cyclooxygenase Inhibitors / adverse effects
  • Cyclooxygenase Inhibitors / pharmacokinetics
  • Cyclooxygenase Inhibitors / therapeutic use
  • Cytochrome P-450 CYP2C9
  • Female
  • Gastrointestinal Diseases / chemically induced*
  • Gastrointestinal Diseases / genetics
  • Gastrointestinal Diseases / metabolism
  • Genetic Predisposition to Disease
  • Genotype
  • Glucuronosyltransferase / genetics
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • UDP-glucuronosyltransferase, UGT1A6
  • Glucuronosyltransferase
  • Aspirin