Polymorphisms in Genes Encoding Acetylsalicylic Acid Metabolizing Enzymes Are Unrelated to Upper Gastrointestinal Health in Cardiovascular Patients on Acetylsalicylic Acid

Overview

Journal Br J Clin Pharmacol

Specialty Pharmacology

Date 2005 Nov 25

PMID 16305586

Citations 5

Authors

Martijn G H van Oijen

Sylvie Huybers

Wilbert H M Peters

Joost P H Drenth

Robert J F Laheij

Freek W A Verheugt

Jan B M J Jansen

Affiliations

Soon will be listed here.

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.

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References

Lapple F, von Richter O, Fromm M, Richter T, Thon K, Wisser H . Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003; 13(9):565-75. DOI: 10.1097/00008571-200309000-00005. View

Verlaan M, Te Morsche R, Pap A, Laheij R, Jansen J, Peters W . Functional polymorphisms of UDP-glucuronosyltransferases 1A1, 1A6 and 1A8 are not involved in chronic pancreatitis. Pharmacogenetics. 2004; 14(6):351-7. DOI: 10.1097/00008571-200406000-00004. View

Lanas A, Serrano P, Bajador E, Esteva F, Benito R, Sainz R . Evidence of aspirin use in both upper and lower gastrointestinal perforation. Gastroenterology. 1997; 112(3):683-9. DOI: 10.1053/gast.1997.v112.pm9041228. View

Strassburg C, Oldhafer K, Manns M, Tukey R . Differential expression of the UGT1A locus in human liver, biliary, and gastric tissue: identification of UGT1A7 and UGT1A10 transcripts in extrahepatic tissue. Mol Pharmacol. 1997; 52(2):212-20. DOI: 10.1124/mol.52.2.212. View

Verheugt F . Aspirin, the poor man's statin?. Lancet. 1998; 351(9098):227-8. DOI: 10.1016/S0140-6736(05)78280-5. View

Revicki D, Wood M, Wiklund I, Crawley J . Reliability and validity of the Gastrointestinal Symptom Rating Scale in patients with gastroesophageal reflux disease. Qual Life Res. 1998; 7(1):75-83. DOI: 10.1023/a:1008841022998. View

Schoenfeld P, Kimmey M, Scheiman J, Bjorkman D, Laine L . Review article: nonsteroidal anti-inflammatory drug-associated gastrointestinal complications--guidelines for prevention and treatment. Aliment Pharmacol Ther. 1999; 13(10):1273-85. DOI: 10.1046/j.1365-2036.1999.00617.x. View

Tukey R, Strassburg C . Genetic multiplicity of the human UDP-glucuronosyltransferases and regulation in the gastrointestinal tract. Mol Pharmacol. 2001; 59(3):405-14. DOI: 10.1124/mol.59.3.405. View

Bigler J, Whitton J, Lampe J, Fosdick L, Bostick R, Potter J . CYP2C9 and UGT1A6 genotypes modulate the protective effect of aspirin on colon adenoma risk. Cancer Res. 2001; 61(9):3566-9. View

10.

Verheugt F, Gersh B . Aspirin beyond platelet inhibition. Am J Cardiol. 2002; 90(1):39-41. DOI: 10.1016/s0002-9149(02)02383-4. View

11.

Pascussi J, Gerbal-Chaloin S, Drocourt L, Maurel P, Vilarem M . The expression of CYP2B6, CYP2C9 and CYP3A4 genes: a tangle of networks of nuclear and steroid receptors. Biochim Biophys Acta. 2003; 1619(3):243-53. DOI: 10.1016/s0304-4165(02)00483-x. View

12.

Laheij R, van Rossum L, Krabbe P, J B M J Jansen , Verheugt F . The impact of gastrointestinal symptoms on health status in patients with cardiovascular disease. Aliment Pharmacol Ther. 2003; 17(7):881-5. DOI: 10.1046/j.1365-2036.2003.01542.x. View

13.

Laheij R, van Rossum L, J B M J Jansen , Verheugt F . Proton-pump inhibitor therapy for acetylsalicylic acid associated upper gastrointestinal symptoms: a randomized placebo-controlled trial. Aliment Pharmacol Ther. 2003; 18(1):109-15. DOI: 10.1046/j.1365-2036.2003.01656.x. View

14.

Strassburg C, Manns M, Tukey R . Expression of the UDP-glucuronosyltransferase 1A locus in human colon. Identification and characterization of the novel extrahepatic UGT1A8. J Biol Chem. 1998; 273(15):8719-26. DOI: 10.1074/jbc.273.15.8719. View

15.

Petty G, Brown Jr R, Whisnant J, Sicks J, OFallon W, Wiebers D . Frequency of major complications of aspirin, warfarin, and intravenous heparin for secondary stroke prevention. A population-based study. Ann Intern Med. 1999; 130(1):14-22. DOI: 10.7326/0003-4819-130-1-199901050-00004. View

16.

Lampe J, Bigler J, Horner N, Potter J . UDP-glucuronosyltransferase (UGT1A1*28 and UGT1A6*2) polymorphisms in Caucasians and Asians: relationships to serum bilirubin concentrations. Pharmacogenetics. 1999; 9(3):341-9. DOI: 10.1097/00008571-199906000-00009. View