The influence of 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene promoter on the incidence, growth and operative risk of abdominal aortic aneurysm.
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.
Jones
K
K
Imperial College at Charing Cross, St Dunstans Road, London W6 8RP, U.K.
Powell
J
J
Brown
L
L
Greenhalgh
R
R
Jormsjö
S
S
Eriksson
P
P
D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics* / Q000401:mortality / Q000601:surgery*; D003404:Creatinine / Q000097:blood; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology; D014656:Vascular Surgical Procedures
D017395:Plasminogen Activator Inhibitor 1; D003404:Creatinine