Genetics Of Aortic Dissection

The understanding of the underlying genetic disorders to aortic dissection remain to be addressed. Numerous genetic disorders with aortic phenotypes have been reported, which may add insight to our understanding of specific facets of genetic mutations linked with aortic dissection40. One notable disease is the connective tissue disorder, Marfan's syndrome, which is associated with manifestation of aortic dissection and which is linked with mutations in the fibrillin genes41. It is most likely that instability of the aortic structure is the main pathology associated with aortic dissection in Marfan's syndrome. Supravalvular aortic stenosis is associated with the elastin gene and Ehlers-Danlos syndrome (type I) with the procollagen gene for other diseases in which disorders of genes associated with structural integrity of the aortic wall may show a possible link42. Familial aortic aneurysms have been reported to be linked to the procollagen and fibrillin-1 genes43. Other remote possibilities include the PKD-1 gene, which is associated with polycystic kidney disease (which may manifest aortic disease), the endoglin gene (which is associated with hereditary hemorrhagic teleangiectasia), and HLA B-27/Dw-12/B52 (which have been implicated in aortic inflammation).

Numerous families with aortic dissection have been reported. The study of such families may be the key to finding the susceptible genes involved. One study narrowed the linkage to a locus at 5q13-14, but none of the known genes—which included Versican (encoding a proteoglycan found in the ECM), thrombospondin (encoding an extracellular Ca-binding protein), and CRTL (encoding a cartilage link protein)—were accountable for the disease44. Another locus has been mapped to 3p24-25, which overlaps a previously mapped second locus for Marfan's syndrome named the MFS locus41. Further investigation will be necessary to determine whether there is a link. The chromosome 11q23.2-q24 has also been shown to be a locus for familial aortic aneurysm disease45. Perhaps there is an unknown gene associated with aortic dissection, but further investigations will be necessary to dissect the genes directly involved in aortic dissection.

Such studies suggesting association of genes associated with aortic stability will provide important insight into at least one of the facets of the disease as will do studies linking monogenic abnormalities. However, given the multifac-torial nature of aortic dissection (including acquired changes of the wall due to atherosclerosis and hypertension in addition to multigenic associations), how the complicated regulation by environmental cues on top of genetic abnormalities increases specific risk for the disease will be the ultimate question that needs to be answered.

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