title: Matrix metalloproteinase-9 genotype as a potential genetic marker for abdominal aortic aneurysm.
abstract: BACKGROUND
  Degradation of extracellular matrix support in the large abdominal arteries contribute to abnormal dilation of aorta, leading to abdominal aortic aneurysms, and matrix metalloproteinase-9 (MMP-9) is the predominant enzyme targeting elastin and collagen present in the walls of the abdominal aorta. Previous studies have suggested a potential association between MMP-9 genotype and abdominal aortic aneurysm, but these studies have been limited only to the p-1562 and (CA) dinucleotide repeat microsatellite polymorphisms in the promoter region of the MMP-9 gene. We determined the functional alterations caused by 15 MMP-9 single-nucleotide polymorphisms (SNPs) reported to be relatively abundant in the human genome through Western blots, gelatinase, and promoter-reporter assays and incorporated this information to perform a logistic-regression analysis of MMP-9 SNPs in 336 human abdominal aortic aneurysm cases and controls.
  
  
  RESULTS
  Significant functional alterations were observed for 6 exon SNPs and 4 promoter SNPs. Genotype analysis of frequency-matched (age, sex, history of hypertension, hypercholesterolemia, and smoking) cases and controls revealed significant genetic heterogeneity exceeding 20% observed for 6 SNPs in our population of mostly white subjects from Northern Wisconsin. A step-wise logistic-regression analysis with 6 functional SNPs, where weakly contributing confounds were eliminated using Akaike information criteria, gave a final 2 SNP (D165N and p-2502) model with an overall odds ratio of 2.45 (95% confidence interval, 1.06-5.70).
  
  
  CONCLUSIONS
  The combined approach of direct experimental confirmation of the functional alterations of MMP-9 SNPs and logistic-regression analysis revealed significant association between MMP-9 genotype and abdominal aortic aneurysm.
authors.affiliation: Molecular and Cellular Pharmacology Graduate Program, University of Wisconsin School of Medicine and Public Health, 1300 University Ave, Madison, WI 53706, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Duellman
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Warren
authors.forename: Peggy
authors.initials: P
authors.lastname: Peissig
authors.forename: Martha
authors.initials: M
authors.lastname: Wynn
authors.forename: Jay
authors.initials: J
authors.lastname: Yang
mesh_terms: D017544:Aortic Aneurysm, Abdominal / Q000235:genetics*; D016022:Case-Control Studies; D003710:Demography; D005091:Exons; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D020780:Matrix Metalloproteinase 9