title: Polymorphisms in dipeptidyl peptidase IV gene are associated with the risk of myocardial infarction in patients with atherosclerosis.
abstract: BACKGROUND
  Dipeptidyl peptidase IV (DPP-IV) is not only important in pancreatic β-cell regulation but also has proinflammatory actions that can contribute to atherosclerosis progression. Previously, we showed that DPP-IV is co-localized with CD31 (an endothelial cell marker) in the neovessels within the human atherosclerotic plaques. These characteristics of DPP-IV may predispose patients with coronary artery disease (CAD) to plaque rupture and thus to myocardial infarction. The goal of this investigation was to determine whether genetic alterations in DPP-IV predispose to plaque vulnerability and myocardial infarction (MI).
  
  
  METHODS
  Between Aug 2004, and March 2007, blood samples of patients (age <60) with angiographically documented CAD were collected. Demographic, clinical, risk factor, and angiographic data were recorded. Eight hundred and seventy five patients of European ancestry with angiographic CAD were divided into those with MI (n=421) and those without (n=454). A genome-wide association study was performed using the Affymetrix 6.0 chip to identify loci that predispose to MI. In the current study we only focused on DPP4 gene to assess the association of single nucleotide polymorphisms (SNPs) in the DPP-IV gene and risk of MI in patients with CAD. For genotyped SNPs, association was tested by logistic regression with significance level of 0.05. Plasma DPP-IV level was measured using a commercial ELISA kit.
  
  
  RESULTS
  Average patients' age at diagnosis of CAD was 46.8years for MI group and 50.8 in the non MI group. There was no difference in distribution of traditional risk factors between the two groups. We identified one SNP (rs3788979) that was significantly related to angiographic CAD with MI, vs. without MI (OR: 1.36, p=0.03). The association of the identified SNP to MI risk was not attenuated after adjustment for traditional risk factors. The SNP was associated with lower levels of plasma DPP-IV (p=0.005). Moreover, CAD patients with the major alleles (GG) and no MI had highest plasma DPP-IV levels. (481.6, p=0.002).
  
  
  CONCLUSIONS
  A polymorphism in the DPP-IV gene in patients with known CAD may increase the risk of MI. This SNP is associated with decreased plasma DPP4 level in patients with MI.
authors.affiliation: Tufts Medical Center, Department of Cardiovascular Disease, 800 Washington St., Boston, MA, United States. naghili@tuftsmedicalcenter.org
authors.forename: Nima
authors.initials: N
authors.lastname: Aghili
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Devaney
authors.forename: Lee O
authors.initials: LO
authors.lastname: Alderman
authors.forename: Zofia
authors.initials: Z
authors.lastname: Zukowska
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Epstein
authors.forename: Mary Susan
authors.initials: MS
authors.lastname: Burnett
mesh_terms: D000483:Alleles; D050197:Atherosclerosis / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000235:genetics; D004247:DNA / Q000235:genetics; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000473:pathology; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D040081:Protein Array Analysis; D012306:Risk
chemical_list: D004247:DNA; D018819:Dipeptidyl Peptidase 4