Association of 1166A>C AT 1 R,-1562C>T MMP-9,ACE I/D,and CCR5 Δ32 Polymorphisms with Abdominal Aortic Aneurysm in Croatian Patients

Abstract

Aim: 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.