BACKGROUND: a single base pair deletion/insertion (4G/5G) polymorphism in the plasminogen activator inhibitor (PAI-1) promoter appears to influence PAI-1 synthesis (increased PAI-1 and inhibition of fibrinolysis with the 4G allele) and survival after severe trauma. OBJECTIVE: to identify whether the 4G/5G polymorphism influences the natural history of abdominal aortic aneurysm (AAA). METHODS:Four hundred and sixty patients with small AAA were genotyped for the 4G/5G polymorphism. AAA growth was assessed from serial ultrasonographic measurements, subject to linear regression analysis. Mortality following eventual elective surgery was recorded. RESULTS: the frequency of the 3 genotypes (4G4G, 4G5G and 5G5G) was in Hardy-Weinberg equilibrium and similar to that in a healthy population. The mean aneurysm growth rate was 0.37, 0.35 and 0.44 cm/year respectively for patients of 4G4G, 4G5G and 5G5G genotype respectively, p = 0.07. The 30d mortality following open elective aneurysm repair was 8% (7/87), 8% (11/145) and 0% (0/56) for patients of 4G4G, 4G5G and 5G5G genotype respectively, giving a higher mortality for those carrying a 4G allele p = 0.03. CONCLUSIONS: polymorphism of the PAI-1 gene promoter does not influence the development of AAA, although AAA growth is faster for patients of 5G5G genotype. However, this genotype (5G5G), which is associated with enhanced fibrinolysis, appears protective following open aneurysm repair. This effect of PAI-1 genotype on survival following surgery is likely to have widespread significance in vascular and general surgery. Copyright 2002 Elsevier Science Ltd.
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BACKGROUND: a single base pair deletion/insertion (4G/5G) polymorphism in the plasminogen activator inhibitor (PAI-1) promoter appears to influence PAI-1 synthesis (increased PAI-1 and inhibition of fibrinolysis with the 4G allele) and survival after severe trauma. OBJECTIVE: to identify whether the 4G/5G polymorphism influences the natural history of abdominal aortic aneurysm (AAA). METHODS: Four hundred and sixty patients with small AAA were genotyped for the 4G/5G polymorphism. AAA growth was assessed from serial ultrasonographic measurements, subject to linear regression analysis. Mortality following eventual elective surgery was recorded. RESULTS: the frequency of the 3 genotypes (4G4G, 4G5G and 5G5G) was in Hardy-Weinberg equilibrium and similar to that in a healthy population. The mean aneurysm growth rate was 0.37, 0.35 and 0.44 cm/year respectively for patients of 4G4G, 4G5G and 5G5G genotype respectively, p = 0.07. The 30d mortality following open elective aneurysm repair was 8% (7/87), 8% (11/145) and 0% (0/56) for patients of 4G4G, 4G5G and 5G5G genotype respectively, giving a higher mortality for those carrying a 4G allele p = 0.03. CONCLUSIONS: polymorphism of the PAI-1 gene promoter does not influence the development of AAA, although AAA growth is faster for patients of 5G5G genotype. However, this genotype (5G5G), which is associated with enhanced fibrinolysis, appears protective following open aneurysm repair. This effect of PAI-1 genotype on survival following surgery is likely to have widespread significance in vascular and general surgery. Copyright 2002 Elsevier Science Ltd.
Authors: Monica M Dua; Noriyuki Miyama; Junya Azuma; Geoffrey M Schultz; Mien Sho; John Morser; Ronald L Dalman Journal: Surgery Date: 2010-06-19 Impact factor: 3.982