title: New single-nucleotide polymorphisms associated with differences in platelet reactivity and their influence on survival in patients with type 2 diabetes treated with acetylsalicylic acid: an observational study.
abstract: OBJECTIVE
  Genetic polymorphisms may contribute to platelet reactivity in diabetic patients; however, the information on their influence on long-term antiplatelet therapy is lacking. Our aim was to evaluate the role of previously described genetic variants and platelet reactivity on risk of all-cause mortality and cardiovascular events.
  
  
  METHODS
  Blood samples were obtained from 303 Caucasian patients. Genome-wide genotyping was performed using Illumina Human Omni 2.5-Quad microarrays, and individual genotyping of selected SNPs was performed using a custom Sequenom iPLEX assay in conjunction with the Mass ARRAY platform. Platelet reactivity was measured with VerifyNow Aspirin Assay and PFA-100 Assay. Univariate and multivariate Cox regression analyses were performed to determine the impact of genetic variants and platelets reactivity on risk of all-cause mortality and cardiovascular events.
  
  
  RESULTS
  Among the 237 patients included in the follow-up, death from any cause occurred in 34 (14.3%) patients and cardiovascular events occurred in 51 (21.5%) patients within a median observation time of 71 months (5.9 years). In univariate analyses, significant association in the presence of minor alleles in TXBA2R (rs1131882) with primary (HR 2.54, 95% CI 1.15-5.60, p = 0.021) and secondary endpoint (HR 2.06, 95% CI 1.06-4.04, p = 0.034) was observed. In addition, multivariate analyses revealed the impact of this polymorphism on primary (HR 2.34, 95% CI 1.09-5.00, p = 0.029) and secondary endpoint (HR 1.89, 95% CI 1.00-3.57, p = 0.048).
  
  
  CONCLUSIONS
  Results of the study demonstrate for the first time an association between genetic polymorphism within TXBA2R gene encoding platelet's surface receptor and long-term survival of diabetic patients treated with ASA.
authors.affiliation: Department of Experimental and Clinical Pharmacology, Center for Preclinical Research and Technology CEPT, Medical University of Warsaw, Banacha 1B str., 02-097, Warsaw, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Milanowski
authors.affiliation: Department of Experimental and Clinical Pharmacology, Center for Preclinical Research and Technology CEPT, Medical University of Warsaw, Banacha 1B str., 02-097, Warsaw, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Pordzik
authors.affiliation: Perioperative Genomics Laboratory, College of Medicine, Penn State University, Hershey, PA, USA.
authors.forename: Piotr K
authors.initials: PK
authors.lastname: Janicki
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 Cardiology and Hypertension, Central Clinical Hospital, Ministry of the Interior, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Rosiak
authors.affiliation: Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Peller
authors.affiliation: Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Tyminska
authors.affiliation: Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Ozieranski
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, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Opolski
authors.affiliation: Department of Experimental and Clinical Pharmacology, Center for Preclinical Research and Technology CEPT, Medical University of Warsaw, Banacha 1B str., 02-097, Warsaw, Poland.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Mirowska-Guzel
authors.affiliation: Department of Experimental and Clinical Pharmacology, Center for Preclinical Research and Technology CEPT, Medical University of Warsaw, Banacha 1B str., 02-097, Warsaw, Poland. mpostula@wum.edu.pl.|Perioperative Genomics Laboratory, College of Medicine, Penn State University, Hershey, PA, USA. mpostula@wum.edu.pl.
authors.forename: Marek
authors.initials: M
authors.lastname: Postula
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000483:Alleles; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D000077144:Clopidogrel; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D005838:Genotype; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D015539:Platelet Activation / Q000187:drug effects / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000235:genetics; D016019:Survival Analysis; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D001241:Aspirin; D000077144:Clopidogrel; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013988:Ticlopidine; C000617896:TXBA2 receptor, human
keywords: Acetylsalicylic acid; Diabetes; Genetics; Platelet reactivity