Genotype-phenotype relationships in an investigation of the role of proteases in abdominal aortic aneurysm expansion.
Br J Surg
; 92(11): 1372-6, 2005 Nov.
Article
em En
| MEDLINE
| ID: mdl-16082623
ABSTRACT
BACKGROUND:
The aim of the study was to investigate the effect of functional polymorphisms in promoters of matrix metalloproteinase (MMP) 2, MMP-3, MMP-9, MMP-12 and plasminogen activator inhibitor (PAI) 1 genes on the growth rate of small abdominal aortic aneurysms (AAA).METHODS:
Some 455 individuals with a small AAA (4.0-5.5 cm) were monitored for aneurysm growth by ultrasonography (mean follow-up 2.6 years). They also provided a DNA sample for analysis of the -1306 C > T, -1171 5A > 6A, -1562 C > T, -82 A > G and -675 4G > 5G alleles of MMP-2, MMP-3, MMP-9, MMP-12 and PAI-1, respectively. Mean linear AAA growth rates were calculated by flexible modelling; the sample size was sufficient to detect variants that influenced the growth rate by 25 per cent.RESULTS:
For MMP-2, MMP-9 and MMP-12 genotypes, growth rates were similar to the mean linear growth rate of 3.08 mm per year. For MMP-3, growth rates were 3.05 (for 5A5A), 3.19 (for 5A6A) and 2.90 (for 6A6A) mm per year. For PAI-1, patients with 4G4G, 4G5G and 5G5G genotypes had growth rates of 3.18, 2.92 and 3.47 mm per year, respectively, for aneurysms with a baseline diameter of 45.1, 44.6 and 46.2 mm. The increased growth rate for patients with PAI-1 5G5G genotype was not statistically significant (P = 0.061), although these patients had the lowest plasma PAI-1 concentrations (P = 0.018).CONCLUSION:
There was no evidence that any specific MMP polymorphism had a clinically significant effect on AAA expansion. The plasminogen system may have a small but clinically significant role in AAA development. Much larger studies would be needed to evaluate genes of smaller effect.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidor 1 de Ativador de Plasminogênio
/
Aneurisma da Aorta Abdominal
/
Metaloproteinases da Matriz
Tipo de estudo:
Clinical_trials
Limite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Br J Surg
Ano de publicação:
2005
Tipo de documento:
Article