title: Genotype-phenotype relationships in an investigation of the role of proteases in abdominal aortic aneurysm expansion.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Eriksson
authors.forename: S
authors.initials: S
authors.lastname: Jormsjö-Pettersson
authors.forename: A R
authors.initials: AR
authors.lastname: Brady
authors.forename: H
authors.initials: H
authors.lastname: Deguchi
authors.forename: A
authors.initials: A
authors.lastname: Hamsten
authors.forename: J T
authors.initials: JT
authors.lastname: Powell
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D020782:Matrix Metalloproteinases