title: Association of 1166A>C AT1R, -1562C>T MMP-9, ACE I/D, and CCR5Δ32 Polymorphisms with Abdominal Aortic Aneurysm in Croatian Patients.
abstract: OBJECTIVE
  The purpose of this case-control study was to assess the association of abdominal aortic aneurysm (AAA) in Croatian patients with four genetic polymorphisms: SNP 1166A>C in the angiotensin II type 1 receptor gene (AT1R); SNP -1562C>T in the matrix metalloproteinase-9 gene (MMP-9); the deletion of 32 bp in the chemokine receptor 5 gene (CCR5); and the insertion/deletion (I/D) of 287 bp in the angiotensin-converting enzyme gene (ACE).
  
  
  METHODS
  Case-control study conducted with 117 patients with confirmed AAA (AAA+) and 117 control subjects (AAA-). Genotyping was performed using PCR or PCR-RFLP analysis. Statistical analyses were performed using MedCalc 12.1 software.
  
  
  RESULTS
  The deletion of 287 bp in the ACE gene (allele D) was more frequently found among AAA+patients than AAA-subjects (66.7% vs. 47.9%, p = 0.0001), due principally to a higher percentage of DD homozygotes (46.2% vs. 15.4%, p < 0.0001). The associated increased risk for AAA was detected in both the nonadjusted recessive model of inheritance (odds ratio [OR] = 3.00, 95% confidence interval [CI] = 1.88-4.79, p = < 0.0001) and when adjusted for age, sex, smoking, hypertension, and hyperlipidemia (OR = 4.96; 95% CI = 1.68-14.59, p = 0.004). The adjusted recessive models also showed increased risk for AAA for the carriers of MMP-9 T allele (OR = 15.69, 95% CI = 1.40-175.41, p = 0.025). Patients with small aneurysms compared with those with large ones were more frequent carriers of the AT1R allele C (37.8% vs. 23.2%, p = 0.029), and logistic regression analysis showed decreased risk for developing large aneurysms in both adjusted models, dominant and recessive (OR = 0.3929, 95% CI = 0.1554-0.9932, p = 0.0483 and OR = 0.1728, 95% CI = 0.0331-0.9023; p = 0.0374, respectively). No difference among any type of the studied groups or subgroups was observed regarding the CCR5Δ32 polymorphism.
  
  
  CONCLUSIONS
  ACE I/D is associated with AAA, and 1166A>C AT1R with the size of the aneurysm, while -1562C>T MMP-9 and CCR5Δ32 polymorphisms are most probably not associated with AAA in Croatian patients.
authors.affiliation: 1 Division of Vascular Surgery, Clinical Department of Surgery, University Hospital Center Zagreb , Zagreb, Croatia .
authors.forename: Andrea
authors.initials: A
authors.lastname: Crkvenac Gregorek
authors.affiliation: 2 Division of Cytogenetics, Clinical Department for Laboratory Diagnostics, University Hospital Center Zagreb , Zagreb, Croatia .
authors.forename: Kristina Crkvenac
authors.initials: KC
authors.lastname: Gornik
authors.affiliation: 3 Fidelta Ltd for Research and Development , Zagreb, Croatia .
authors.forename: Darija Stupin
authors.initials: DS
authors.lastname: Polancec
authors.affiliation: 4 Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Zagreb , Zagreb, Croatia .
authors.forename: Sanja
authors.initials: S
authors.lastname: Dabelic
mesh_terms: D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics*; D017523:Croatia; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics*
chemical_list: C584933:CCR5 protein, human; D044140:Receptor, Angiotensin, Type 1; D019713:Receptors, CCR5; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: ACE; AT1R; CCR5; MMP-9; aneurysm; polymorphism