Table 2.

Non-syndromic genetic associations with thoracic aortic aneurysms and dissections.

Gene loci	Association	Presentation	Pathophysiology
FBN1 (16)	Present in 3.9% of non-syndromic TAD	TAAD	Affect ECM microfibrils and causes sporadic TAD in non-Marfan patients
FOXE3 (30)	Autosomal dominant inheritance	TAAD	Reduced SMC density through impairing development and increasing apoptosis
LOX (34, 35)	Genetic predisposition in 25% of familial TAAD	TAAD	Deficiency of LOX or inhibition of lysyl oxidases
MAT2A (31)	Strong familial association	TAAD	Defective MAT IIA enzyme impairs methylation reactions in SMC
MFAP5 (32)	Strong familial association	TAAD	Mutation dysregulates TGFB/BMP signalling pathway
MYH11 (36)	Strong familial association	TAAD	Upregulation of IGF-1 and angiotensin II without increased TGFB
MYLK (37)	Strong familial association	TAD	Disruption of calmodulin and kinase activity of SMC
PRKG1 (38, 39)	Strong familial association	TAD	Increased PKG1 decreases contractility of aorta SMC
SMAD3 (40)	Responsible for 2% of TAAD	TAAD	SMAD3 haploinsufficiency disrupts differentiation and collagenous function of myofibroblasts
AAT1/FAA1 (41)	Genetic predisposition	TAAD	Identified association with loci at chromosome 11q23.2-q24
AAT2/TAAD1 (42)	Genetic predisposition	TAAD	Identified association with loci at chromosome 5q13-14
Unidentified gene (43)	Genetic predisposition	TAAD	Marfan-like condition associated with loci at chromosome 3p24-25

SMC, smooth muscle cell; TAA, thoracic aortic aneurysm; TAD, thoracic aortic dissection; PKG-1, type I cGMP-dependent protein kinase.