Growth Rate of Small Abdominal Aortic Aneurysms and Genetic Polymorphisms of Matrix MetalloProteases-1, -3, and -9

Genetic variants of matrix metalloproteases (MMPs)-1, -3, and 9, together with clinical variables, might predict the growth rate (GR) of abdominal aortic aneurysm (AAA). Genotyping of MMP-1 (-1,607 G+/G-), MMP-3 (- 1,171 6A/5A), and MMP-9 microsatellite (13-26 cytosine-adenosine repeats around -90) from peripheral blood was performed in 137 AAA patients with two AAA diameter measurements (at least 3 months to 1 year apart). When the same technique (either ultrasound or computed tomography) was used for the two measurements, yearly GR was estimated and compared with MMP genotype and clinical features by linear and binary logistic regression. Collectively, 36 patients provided 94 observations, with a median GR of 3 mm/year (interquartile range, 0-5.8); GRs in carriers of MMP-1 polymorphism G-/G-, G-/G+, and G+/G+ genotype were 0.3, 3.5, and 4.7mm/year, respectively (p = 0.008). In linear logistic regression, the main determinant of GR was growth arrest (GA, i.e., GR = 0, occurring in 32 observations, 34%). In turn, GA occurred mainly in G-/G- MMP-1 genotype (odds ratio, 3.9; 95% confidence interval, 1.6-9.7; p = 0.002), while variables accounting for GR > 0 were MMP-1 G + /G+ genotype, intake of any antihypertensive drug, and MMP-3 6A/6A genotype. Carriers of none, one, or two/three of these conditions accounted for a GR of 3, 4, and 9 mm/year, respectively (p = 0.001). MMP-1 (-1,607 G+/-) variant is associated to differential GR in AAA: homozygous G deletion variant shows higher GA prevalence and lower GR, while carriers of G + /G+ MMP-1 genotype, together with intake of antihypertensive drugs, and 6A/6A in MMP-3 present cumulative GR increase.