A Dab2Ip Genotype: Sex Interaction is Associated with Abdominal Aortic Aneurysm Expansion

Abstract

A faster expansion rate of abdominal aortic aneurysm (AAA) increases the risk of rupture. Women are at higher risk of rupture than men, but the mechanisms underlying this increased risk are unknown. We investigated whether genetic variants that influence susceptibility for AAA (, ,, and) are associated with AAA expansion and whether these associations differ by sex in 650 patients with AAA (mean age 70±8 years, 17% women) enrolled in the Mayo Clinic Vascular Disease Biorepository. Women had a mean aneurysm expansion 0.41 mm/year greater than men after adjustment for baseline AAA size. In addition to baseline size, mean arterial pressure (MAP), non-diabetic status, rs599839[G] andrs7025486[A] were associated with greater aneurysm expansion (all p<0.05). The associations of MAP and rs599839[G] were similar in both sexes, while the associations of baseline size, pulse pressure (PP) and rs7025486[A] were stronger in women than men (all p ≤0.02). A three-way interaction of PP*sex* rs7025486[A] was noted in a full-factorial analysis (p=0.007) independent of baseline size and MAP. In the high PP group (≥median), women had a mean growth rate 0.68 mm/year greater per [A] of rs7025486 than men (p =0.003), whereas there was no difference in the low PP group (p =0.8). We demonstrate that variants rs7025486[A] andrs599839[G] are associated with AAA expansion. The association of rs7025486[A] is stronger in women than men and amplified by high PP, contributing to sex differences in aneurysm expansion.

Gender difference and genetic variance in lipoprotein receptor‑related protein 1 is associated with mortality

“…The present study was able to confirm that the T allele also had an association with mortality, but only in one of the two genders. Ye et al (28) in a study of abdominal aneurysms, demonstrated significant sex differences, where a faster expansion of the aneurysms could be seen in the female group and therefore the present study intended to evaluate any sex differences in CV mortality in the different genotypes of rs1466535.…”

Gender differences in outcomes after aortic aneurysm surgery should foster further research to improve screening and prevention programmes

“…In particular the authors hypothesised that oscillatory shear stress is a specific signal to the endothelium, which initiates the events leading to AAA formation, and that sex-dependent differences in oscillatory shear stress in the infrarenal aorta may explain the gender-related differences. Ye et al 39 investigated the potential influence of genetic variants on susceptibility to AAAs (CDKN2A-2B, SORT1, DAB2IP, LRP1 and LDLR), and their association (particularly gender-related) with AAA expansion. In a population of 650 patients affected by AAA, the authors demonstrated that women had a mean greater aneurysm expansion than men after adjustment for baseline AAA diameter.…”

“…Ye et al. 39 investigated the potential influence of genetic variants on susceptibility to AAAs (CDKN2A-2B, SORT1, DAB2IP, LRP1 and LDLR), and their association (particularly gender-related) with AAA expansion. In a population of 650 patients affected by AAA, the authors demonstrated that women had a mean greater aneurysm expansion than men after adjustment for baseline AAA diameter.…”

Association of Genetic Polymorphisms with Abdominal Aortic Aneurysm in the Processes of Apoptosis, Inflammation, and Cholesterol Metabolism

“…It mainly occurs in the last decades of life and predominantly affects the male gender [2]. A ruptured AAA leads to a high mortality rate of up to 80% [3,4]. The risk of developing AAA increases with hypertension, dyslipidemia, and a history of smoking [5,6].…”