Genetic risk factor characterizes abdominal aortic aneurysm from arterial occlusive disease in human beings: CCR5 Delta 32 deletion.
OBJECTIVE
Inflammation is involved in the pathogenesis of atherosclerosis and abdominal aortic aneurysm (AAA), and chemokines are mediators of the inflammatory process. The homozygous Delta 32 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 Delta 32 deletion mutation and AAA, peripheral arterial occlusive disease (PAOD), and carotid stenosis.


METHODS
The CCR5 Delta 32 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.


RESULTS
In patients with AAA the Delta 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 Delta 32 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 Delta 32 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).


CONCLUSIONS
CCR5 Delta 32 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.


CONCLUSIONS
The 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 AAs and in patients at poor risk with large AAAs.
Ghilardi
Giorgio
G
Dipartimento MCO, Clinica Chirurgica Generale, Università degli Studi di Milano-Polo Didattico S. Paolo, 9 I-20142 Milano, Italy. giorgio.ghilardi@unimi.it
Biondi
Maria Luisa
ML
Battaglioli
Lodovica
L
Zambon
Antonella
A
Guagnellini
Emma
E
Scorza
Roberto
R
D000368:Aged; D017542:Aneurysm, Ruptured / Q000453:epidemiology / Q000235:genetics; D000792:Angiography; D017544:Aortic Aneurysm, Abdominal / Q000453:epidemiology / Q000235:genetics; D001157:Arterial Occlusive Diseases / Q000453:epidemiology / Q000235:genetics*; D001483:Base Sequence; D016893:Carotid Stenosis / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D011379:Prognosis; D019713:Receptors, CCR5 / Q000235:genetics*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016019:Survival Analysis
D019713:Receptors, CCR5