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27 May 2013

Effect of common single-nucleotide polymorphisms in acetylsalicylic acid metabolic pathway genes on platelet reactivity in patients with diabetes

Marek PostulaABCDEFG, Piotr K. JanickiABCDEFG, Marek RosiakABCDEFG, Agnieszka Kaplon-CieslickaBCD, Agnieszka KondrackaBCD, Ewa TrzeplaBC, Krzysztof J. FilipiakADG, Dariusz A. KosiorADEG, Andrzej CzlonkowskiADEG, Grzegorz OpolskiADG

DOI: 10.12659/MSM.883922

Med Sci Monit 2013; 19:394-408

Abstract

BACKGROUND: Platelet reactivity in patients on acetylsalicylic acid (ASA) therapy can be influenced by physiological or pathological conditions affecting ASA pharmacokinetics or pharmacodynamics. The mechanism of such variability in the therapeutic response to ASA, particularly in diabetic patients, is poorly understood. The rate of elimination of ASA and its metabolite, salicylic acid (SA), is likely a major factor determining drug efficacy. The objective of this study was to investigate the effect of genetic polymorphisms in the selected candidate genes within the ASA metabolic pathway on the platelet reactivity and concentration of ASA and thromboxane A2 (TxA2) metabolites in a population of patients with type 2 diabetes mellitus (T2DM).

MATERIAL AND METHODS: The study cohort consisted of 287 Caucasians with T2DM who had been taking ASA tablets at the dose of 75 mg per day for at least 3 months. Platelet reactivity analyses were performed using VerifyNow Aspirin and PFA-100 assays. The measured ASA metabolite included salicylic acid (ASA), and TxA2 metabolites included serum TxB2 and urinary 11-dh-TxB2. Genotyping for the selected 18 single-nucleotide polymorphisms (SNPs) within 5 genes of the ASA metabolic pathway was performed using a Sequenom iPLEX platform.

RESULTS: No statistically significant association was observed between the investigated SNPs genotypes, platelet reactivity, and measured metabolites in the investigated cohort of patients.

CONCLUSIONS: The results of our study failed to confirm that the selected variants in the genes within the ASA metabolic pathway might contribute to platelet reactivity in a diabetic population treated with ASA.

Keywords: Metabolic Networks and Pathways - genetics, Genotype, Gene Frequency - genetics, Diabetes Mellitus, Type 2 - metabolism, Demography, Blood Platelets - metabolism, Aspirin - metabolism, Polymorphism, Single Nucleotide - genetics

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750