Genes predisposing to rapid aneurysm growth.

The aim of the study was to investigate the effect of functional polymorphisms in promoters of the MMP-2 (-1306 C > T), MMP-3 (-1171 5A > 6A), MMP-9 (-1562 C > T), MMP-12 (-82 A > G), TIMP-1 (-372 C > T), and PAI-1 (-675 4G > 5G and -847 A > G) genes on the growth rate of small abdominal aortic aneurysms. The patients with small aneurysms were recruited from the surveillance arm of the U.K. Small Aneurysm Trial and monitored for aneurysm growth, mean follow-up 2.6 years. Mean linear aneurysm growth rates were calculated by flexible modeling. For MMP-2, MMP-3, MMP-9, MMP-12, and TIMP-1 polymorphisms there were no clear associations with aneurysm growth. The increased growth rates for patients of 5G5G PAI-1 genotype were of borderline significance (P = 0.06). However, PAI-1 haplotype analysis showed that 5G5G/GG patients had significantly faster aneurysm growth (mean 0.46 mm/year faster). There was no evidence that any specific MMP polymorphism had a clinically significant effect on aneurysm growth. However the plasminogen system (via PAI-1) appears to have a small, but clinically significant, role in aneurysm growth.