Analysis of multiple genetic polymorphisms in aggressive-growing and slow-growing abdominal aortic aneurysms Tyler Duellman, BS, Christopher L. Warren,

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Analysis of multiple genetic polymorphisms in aggressive-growing and slow-growing abdominal aortic aneurysms Tyler Duellman, BS, Christopher L. Warren, PhD, Jon Matsumura, MD, Jay Yang, MD, PhD Journal of Vascular Surgery Volume 60, Issue 3, Pages 613-621.e3 (September 2014) DOI: 10.1016/j.jvs.2014.03.274 Copyright © 2014 Society for Vascular Surgery Terms and Conditions

Fig Analysis of aneurysm growth rates in the abdominal aortic aneurysm (AAA) cohort. A, Maximum aortic diameter from one individual assessed by computed tomography (CT; square) and ultrasound imaging (circle) plotted as a function of age. Both imaging methods gave consistent measurements of the aneurysm growth rate and R2 of the linear regression. B, Maximum aortic diameter vs age is shown for two AAA patients, one with aggressive (Agg; square) and one with slow (circle) growth rates. C, Distribution of growth rates in the present cohort of 141 individuals with serial imaging data of their AAAs. Symbols represent a subset of individuals presenting with an acute AAA rupture (star), repaired by intervention (open circle), and those above the diameter threshold (triangle). The use of a linear curve fitting could result in an underestimate of a curvilinear growth rate reported by some, but our preliminary analysis showed no significant increase in the correlation coefficient (R2 statistics) of exponential over linear curve fit. D, Patient aneurysm growth rate was binned, and a threshold of 3.25 mm/y was set to discriminate between aneurysms with slow-growth and fast-growth rates. Ruptured (regardless of the size or rate of growth) or repaired aneurysms (above the growth rate or diameter threshold) were included in the aggressive-growth rate cohort but not in the double Gaussian fit of the growth rate. Journal of Vascular Surgery 2014 60, 613-621.e3DOI: (10.1016/j.jvs.2014.03.274) Copyright © 2014 Society for Vascular Surgery Terms and Conditions

Supplementary Fig 1 (online only) The five genetic polymorphisms show little linkage disequilibrium (LD). Additional genes chosen for genetic associate studies show minor LD with each other. LD is displayed as the D index, with 0 showing no linkage and 1 indicating perfect linkage. LD for the matrix metalloproteinase-9 (MMP-9) single nucleotide polymorphism (SNP) was reported in Duellman et al (2012).16 ACE, Angiotensin-converting enzyme; AT1R, angiotensin 1 receptor; IL-10, interleukin-10; LRP1, low-density lipoprotein receptor-related protein 1; MTHFR, methyl-tetrahydrofolate reductase. Journal of Vascular Surgery 2014 60, 613-621.e3DOI: (10.1016/j.jvs.2014.03.274) Copyright © 2014 Society for Vascular Surgery Terms and Conditions

Supplementary Fig 2 (online only) Population-dependent variation in the minor allele frequency of genetic variations derived from the International HapMap (Haplotype Mapping) database. The bars are minor allele frequency retrieved from the HapMap database and calculated from the observed genotypes for our local patient cohort (Wisc), of the genes showing significant association with abdominal aortic aneurysm (AAA) based on multivariate logistic regression analysis. ACE, Angiotensin-converting enzyme; AT1R, angiotensin 1 receptor; IL-10, interleukin-10; LRP1, low-density lipoprotein receptor-related protein 1; MMP-9, matrix metalloproteinase-9; MTHFR, methyl-tetrahydrofolate reductase. Journal of Vascular Surgery 2014 60, 613-621.e3DOI: (10.1016/j.jvs.2014.03.274) Copyright © 2014 Society for Vascular Surgery Terms and Conditions