PMID- 23715170 OWN - NLM STAT- MEDLINE DCOM- 20131021 LR - 20211021 IS - 1643-3750 (Electronic) IS - 1234-1010 (Print) IS - 1234-1010 (Linking) VI - 19 DP - 2013 May 27 TI - Effect of common single-nucleotide polymorphisms in acetylsalicylic acid metabolic pathway genes on platelet reactivity in patients with diabetes. PG - 394-408 LID - 10.12659/MSM.883922 [doi] AB - 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 A(2) (TxA(2)) 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 TxA(2) metabolites included serum TxB(2) and urinary 11-dh-TxB(2). 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. FAU - Postula, Marek AU - Postula M AD - Department of Cardiology, Medical University of Warsaw, Warsaw, Poland. FAU - Janicki, Piotr K AU - Janicki PK FAU - Rosiak, Marek AU - Rosiak M FAU - Kaplon-Cieslicka, Agnieszka AU - Kaplon-Cieslicka A FAU - Kondracka, Agnieszka AU - Kondracka A FAU - Trzepla, Ewa AU - Trzepla E FAU - Filipiak, Krzysztof J AU - Filipiak KJ FAU - Kosior, Dariusz A AU - Kosior DA FAU - Czlonkowski, Andrzej AU - Czlonkowski A FAU - Opolski, Grzegorz AU - Opolski G LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20130527 PL - United States TA - Med Sci Monit JT - Medical science monitor : international medical journal of experimental and clinical research JID - 9609063 RN - R16CO5Y76E (Aspirin) SB - IM MH - Aged MH - Aspirin/*metabolism MH - Blood Platelets/*metabolism MH - Demography MH - Diabetes Mellitus, Type 2/*genetics/*metabolism MH - Female MH - Gene Frequency/genetics MH - Genotype MH - Humans MH - Male MH - Metabolic Networks and Pathways/*genetics MH - Polymorphism, Single Nucleotide/*genetics PMC - PMC3670858 EDAT- 2013/05/30 06:00 MHDA- 2013/10/22 06:00 PMCR- 2013/05/27 CRDT- 2013/05/30 06:00 PHST- 2013/05/30 06:00 [entrez] PHST- 2013/05/30 06:00 [pubmed] PHST- 2013/10/22 06:00 [medline] PHST- 2013/05/27 00:00 [pmc-release] AID - 883922 [pii] AID - 10.12659/MSM.883922 [doi] PST - epublish SO - Med Sci Monit. 2013 May 27;19:394-408. doi: 10.12659/MSM.883922.