title: Effect of common single nucleotide polymorphisms in COX-1 gene on related metabolic activity in diabetic patients treated with acetylsalicylic acid.
abstract: BACKGROUND
  The objective of this study was to investigate the effect of common single nucleotide genomic polymorphisms in the cyclooxygenase-1 (COX-1) gene on the thromboxane A2 (TxA2) metabolite concentrations in serum and urine, as well as on prostaglandin F2α (PGF2α) urinary excretion in the diabetic population on acetylsalicylic acid (ASA) therapy.
  
  
  METHODS
  The study cohort consisted of 284 Caucasians with diabetes type 2 who had been taking ASA tablets at the dose of 75 mg/day for at least 3 months. Genotyping for the 4 selected SNPs within the COX-1 gene (two nonsynonymous-coding variants, rs3842787 [C50T, P17L] and rs5789 [C174A, L237M]; and two other synonymous SNPs, rs3842788 [G128A, Q41Q] and rs5788 [C644A]) was performed using the Sequenom iPLEX platform.
  
  
  RESULTS
  No statistically significant results were observed for the investigated SNPs and measured metabolites in the investigated cohort of patients. Statistically significant differences in S-TxB2 could however be observed for rs5788 in the subgroup of patients with very high S-TxB2 concentrations. In particular, more patients who were carriers of the minor allele for this polymorphism were observed in the group with S-TxB2 levels > 95(th) percentile, when compared with similar carriers in the group with S-TxB2 < 95(th) percentile (20% vs. 1.1%, respectively, p < 0.001, Mann-Whitney test).
  
  
  CONCLUSIONS
  The results of our study suggest that the four investigated common SNPs in the COX1 gene are not associated with obviously altered TxA2 metabolism and PGF2α synthesis in the investigated diabetic cohort treated with ASA.
authors.affiliation: Department of Cardiology and Hypertension, Central Clinical Hospital, the Ministry of the Interior, Warsaw, Poland ; Department of Clinical and Experimental Pharmacology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Postula
authors.affiliation: Perioperative Genomics Laboratory, Department of Anesthesiology, Penn State College of Medicine, Hershey, Pennsylvania, USA.
authors.forename: Piotr K
authors.initials: PK
authors.lastname: Janicki
authors.affiliation: Department of Cardiology and Hypertension, Central Clinical Hospital, the Ministry of the Interior, Warsaw, Poland ; Department of Clinical and Experimental Pharmacology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Rosiak
authors.affiliation: Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kaplon-Cieslicka
authors.affiliation: Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kondracka
authors.affiliation: Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Trzepla
authors.affiliation: Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Krzysztof J
authors.initials: KJ
authors.lastname: Filipiak
authors.affiliation: Department of Cardiology and Hypertension, Central Clinical Hospital, the Ministry of the Interior, Warsaw, Poland ; Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Dariusz A
authors.initials: DA
authors.lastname: Kosior
authors.affiliation: Department of Clinical and Experimental Pharmacology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Czlonkowski
authors.affiliation: Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Opolski
keywords: 8-iso-prostaglandin F2α; acetylsalicylic acid; cyclooxygenase-1; diabetes mellitus; thromboxane