Genetic risk factor characterizes abdominal aortic aneurysm from arterial occlusive disease in human beings: CCR5 Δ32 deletion

ObjectiveInflammation is involved in the pathogenesis of atherosclerosis and abdominal aortic aneurysm (AAA), and chemokines are mediators of the inflammatory process. The homozygous Δ32 deletion mutation of the gene of the chemokine receptor CCR5 is a cause of its lack in inflammatory cells. The purpose of this study was to investigate the relationship between CCR5 Δ32 deletion mutation and AAA, peripheral arterial occlusive disease (PAOD), and carotid stenosis.MethodsThe CCR5 Δ32 polymorphism was genotyped in 380 subjects: 70 patients operated on to treat AAA (21 ruptured AAAs, 49 elective repair), 76 patients with PAOD, 62 patients with carotid stenosis, and 172 age-matched and sex-matched healthy control subjects. Risk factors for AAA were considered. Each patient was assessed according to a diagnostic procedure tailored to symptoms at presentation.ResultsIn patients with AAA the Δ allelic variation was significantly different compared with control subjects (P = .002; odds ratio [OR], 2.7; 95% confidence interval [CI], 1.41-5.15). The increased presence of this allele differentiates AAA from both PAOD (P = .017; OR, 2.77; 95% CI, 1.17-6.52) and carotid stenosis (P = .01; OR, 3.47; 95% CI, 1.31-9.11). The presence in the genotype of patients with AAA of at least 1 Δ32 allele is more frequent in ruptured AAAs than in electively repaired AAAs (genotype: OR, 4.04; 95% CI, 1.34-12.1; P = .011; allelic frequency: OR, 2.75; 95% CI, 1.07-7.07; P = .035). Among the patients, multiple regression analysis showed that the Δ32 allele is an independent risk factor for AAA vs PAOD (OR, 3.13; 95% CI, 1.33-7.33; P = .012) and for ruptured AAAs vs electively repaired AAAs (OR, 3.52; 95% CI, 1.01-11.80; P = .045).ConclusionsCCR5 Δ32 deletion mutation is significantly more frequent in patients with AAA than in control subjects and in both patients with PAOD and carotid stenosis, and could be a factor that differentiates AAA from PAOD, and ruptured AAAs from AAAs that can be electively repaired.Clinical relevanceThe major threat of abdominal aortic aneurysm (AAA) is rupture, accounting for extremely high mortality. This occurrence has been correlated to aneurysm size, but it is a common observation that small AAAs can rupture and large AAAs can remain stable for many years. This study was carried out in an attempt to search for genetic markers of aneurysm rupture. Some single nucleotide polymorphisms are implicated in acceleration of transcription for enzymes involved in the inflammatory process and in extracellular matrix remodeling. An association between single nucleotide polymorphisms and aneurysm rupture could enable better selection for surgical indications in patients with small AAAs and in patients at poor risk with large AAAs