Trp719Arg Genetic Variant Increases Risk for Thoracic Aortic Dissection

Background: KIF6 (kinesin family member 6), a protein coded by the gene, serves an important intracellular function to transport organelles along microtubules. In a pilot study, we found that a common Trp719Arg variant increased the propensity of thoracic aortic aneurysms (TAA) to suffer dissection (AD). The present study aims for a definite investigation of the predictive ability of 719Arg vis à vis AD. Confirmatory findings would enhance natural history prediction in TAA.

Methods: 1108 subjects (899 aneurysm and 209 dissection patients) had 719Arg variant status determined.

Results: The 719Arg variant in the gene correlated strongly with occurrence of AD. Specifically, 719Arg positivity (homozygous or heterozygous) was substantially more common in dissectors (69.8%) than non-dissectors (58.5%) ( = 0.003). Odds ratios (OR) for suffering aortic dissection ranged from 1.77 to 1.94 for Arg carriers in various dissection categories. These high OR associations were noted for both ascending and descending aneurysms and for homozygous and heterozygous Arg variant patients. The rate of aortic dissection over time was significantly higher for carriers of the Arg allele ( = 0.004). Additionally, Arg allele carriers were more likely to reach the combined endpoint of dissection or death ( = 0.03).

Conclusions: We demonstrate the marked adverse impact of the 719Arg variant of the gene on the likelihood that a TAA patient will suffer aortic dissection. Clinical assessment of the variant status of this molecularly important gene may provide a valuable "non-size" criterion to enhance surgical decision making above and beyond the currently used metric of aortic size (diameter).