title: Analysis of multiple genetic polymorphisms in aggressive-growing and slow-growing abdominal aortic aneurysms.
abstract: BACKGROUND
  The natural history of abdominal aortic aneurysms (AAAs) suggests that some remain slow in growth rate whereas many develop a more accelerated growth rate and reach a threshold for intervention. We hypothesized that different mechanisms are responsible for AAAs that remain slow growing and never become actionable vs the aggressive AAAs that require intervention and may be reflected by distinct associations with genetic polymorphisms.
  
  
  METHODS
  AAA growth rate was determined from serial imaging data in 168 control and 141 AAA patients with ultrasound or computed tomography imaging studies covering ∼5 years. Genetic polymorphisms all previously reported as showing a significant correlation with AAA with functional effects on the expression or function were determined by analysis of the genomic DNA, including angiotensin 1 receptor (rs5186), interleukin-10 (IL-10; rs1800896), methyl-tetrahydrofolate reductase (rs1801133), low-density lipoprotein receptor-related protein 1 (LRP1; rs1466535), angiotensin-converting enzyme (rs1799752), and several matrix metalloproteinase 9 (MMP-9) single nucleotide polymorphisms.
  
  
  RESULTS
  Of the AAA patients, 81 were classified as slow AAA growth rate (<3.25 mm/y) vs 60 with aggressive AAA growth rate (>3.25 mm/y, those presenting with a rupture, or those with maximal aortic diameter >5.5 cm [male] or >5.0 cm [female]). Discriminating confounds between the groups were identified by logistic regression. Analyses identified MMP-9 p-2502 single nucleotide polymorphism (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.31-0.94; P = .029) as a significant confound discriminating between control vs slow-growth AAA, MMP-9 D165N (OR, 0.49; 95% CI, 0.26-0.95; P = .035) and LRP1 (OR, 4.99; 95% CI, 1.13-22.1; P = .034) between control vs aggressive-growth AAAs, and methyltetrahydrofolate reductase (OR, 2.99; 95% CI, 1.01-8.86; P = .048), MMP-9 p-2502 (OR, 2.19; 95% CI, 1.05-4.58; P = .037), and LRP1 (OR, 4.96; 95% CI, 1.03-23.9; P = .046) as the statistically significant confounds distinguishing slow-growth AAAs vs aggressive-growth AAAs.
  
  
  CONCLUSIONS
  Logistic regression identified different genetic confounds for the slow-growth and aggressive-growth AAAs, indicating a potential for different genetic influences on AAAs of distinct aggressiveness. Future logistic regression studies investigating for potential genetic or clinical confounds for this disease should take into account the growth rate and size of the AAA to better identify confounds likely to be associated with aggressive AAAs likely to require intervention.
authors.affiliation: Molecular and Cellular Pharmacology Graduate Program, University of Wisconsin School of Medicine and Public Health, Madison, Wisc.
authors.forename: Tyler
authors.initials: T
authors.lastname: Duellman
authors.affiliation: Proteovista LLC, Madison, Wisc.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Warren
authors.affiliation: Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisc.
authors.forename: Jon
authors.initials: J
authors.lastname: Matsumura
authors.affiliation: Molecular and Cellular Pharmacology Graduate Program, University of Wisconsin School of Medicine and Public Health, Madison, Wisc; Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisc. Electronic address: jyang75@wisc.edu.
authors.forename: Jay
authors.initials: J
authors.lastname: Yang
mesh_terms: D000368:Aged; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging / Q000235:genetics*; D001019:Aortic Rupture / Q000000981:diagnostic imaging / Q000235:genetics*; D001027:Aortography / Q000379:methods; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015986:Confounding Factors, Epidemiologic; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012307:Risk Factors; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014463:Ultrasonography