title: The rs12526453 Polymorphism in an Intron of the PHACTR1 Gene and Its Association with 5-Year Mortality of Patients with Myocardial Infarction.
abstract: OBJECTIVE
  The rs12526453 (C/G) is a single nucleotide polymorphism in an intron of the PHACTR1 gene (phosphatase and actin regulator 1). The C allele is associated with increased risk of coronary artery disease in an unknown mechanism. We investigated its association with long-term overall mortality in patients with ST-elevation myocardial infarction (STEMI) treated invasively.
  
  
  METHODS
  Two independent groups of patients with STEMI were analyzed: a derivation group (n= 638) and a validation one (n=348). Genotyping was performed with the TaqMan method. The analyzed end-point was total long term mortality. Additionally, transcriptomic analysis was performed in mononuclear blood leukocytes from rs12526453 CC monozygotes or G allele carriers.
  
  
  RESULTS
  In the study group (mean age 62.3 ± 11.9 years; 24.9% of females, n=159), percentages of CC, CG, and GG genotypes were 45.3% (n=289), 44.7% (n=285), and 10% (n=64), respectively. In the 5-year follow-up 105 patients died (16.46%). CC homozygotes had significantly lower mortality compared to other genotypes: 13.1% (n=38) vs. 18.3% in G-allele carriers (n=67), (p=0.017, Cox`s F test). In the validation group 47 patients died within 3 years (13.5%). We confirmed lower mortality of CC homozygotes: 10.1 % (n=18) vs. 16.95% in G-allele carriers (n=29), (p=0.031, Cox`s F test). Transcriptomic analysis revealed a markedly higher expression of NLRP-2 in CC homozygotes.
  
  
  CONCLUSIONS
  The rs12526453 CC homozygotes (previously associated with increased risk of myocardial infarction) showed, in 2 independent samples, better long-term survival. The finding of such high effect size, after appropriate validation, could potentially be translated into clinical practice.
authors.affiliation: Department of Cardiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Szpakowicz
authors.affiliation: 1st Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland; Department of Cardiology and Internal Diseases, Military Institute of Medicine, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Kiliszek
authors.affiliation: Department of Forensic Medicine, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Witold
authors.initials: W
authors.lastname: Pepinski
authors.affiliation: Department of Cardiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Waszkiewicz
authors.affiliation: Laboratory of Molecular Biology, The Cardinal Stefan Wyszynski Institute of Cardiology, Warsaw, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Franaszczyk
authors.affiliation: Department of Forensic Medicine, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Skawronska
authors.affiliation: Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Ploski
authors.affiliation: Department of Forensic Medicine, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Niemcunowicz-Janica
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Burzynska
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Tulacz
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Maciejak
authors.affiliation: Department of Cardiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Marcin Jakub
authors.initials: MJ
authors.lastname: Kaminski
authors.affiliation: 1st Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Opolski
authors.affiliation: Department of Cardiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Wlodzimierz Jerzy
authors.initials: WJ
authors.lastname: Musial
authors.affiliation: Department of Cardiology, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Karol Adam
authors.initials: KA
authors.lastname: Kaminski
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D007438:Introns; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016019:Survival Analysis
chemical_list: D008840:Microfilament Proteins; C570134:PHACTR1 protein, human