A DAB2IP genotype: sex interaction is associated with abdominal aortic aneurysm expansion

作者：Ye Zi; Austin Erin; Schaid Daniel J; Bailey Kent R; Pellikka Patricia A; Kullo Iftikhar J

来源：Journal of Investigative Medicine, 2017, 65(7): 1077-1082.

DOI：10.1136/jim-2016-000404

<jats:p>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 (<jats:italic>CDKN2A-2B</jats:italic>,<jats:italic>SORT1</jats:italic>,<jats:italic>DAB2IP</jats:italic>,<jats:italic>LRP1</jats:italic>and<jats:italic>LDLR</jats:italic>) 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,<jats:italic>SORT1-</jats:italic>rs599839[G] and<jats:italic>DAB2IP-</jats:italic>rs7025486[A] were associated with greater aneurysm expansion (all p&lt;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<jats:italic>-</jats:italic><jats:sub>sex<jats:italic>interaction</jats:italic></jats:sub>≤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<jats:italic>-</jats:italic><jats:sub>sex<jats:italic>interaction</jats:italic></jats:sub>=0.003), whereas there was no difference in the low PP group (p<jats:italic>-</jats:italic><jats:sub>sex<jats:italic>interaction</jats:italic></jats:sub>=0.8). We demonstrate that variants<jats:italic>DAB2IP-</jats:italic>rs7025486[A] and<jats:italic>SORT1-</jats:italic>rs599839[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.</jats:p>

• 出版日期2017-10