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.