Association of gene polymorphisms in MYH11 and TGF-β signaling with the susceptibility and clinical outcomes of Debakey type Ⅲ aortic dissection

Abstract Background: Myosin heavy chain 11 (MYH11) and transforming growth factor-β (TGF-β) signaling-related genes as the regulation of the structure and function of vascular smooth muscle cells (VSMCs) play a key role in the pathogenesis of aortic dissection (AD). This study aims to investigate the association of MYH11 and TGF-β signaling-related gene polymorphisms with the susceptibility of DeBakey type III AD and its clinical outcomes. Methods: A total of 159 patients with DeBakey Ⅲ AD and 305 healthy subjects were enrolled in this study. 4 SNPs (MYH11 rs115364997, rs117593370, TGFB1 rs1800469 and TGFBR1 rs1626340) were selected and analyzed. GMDR was used to evaluate gene-gene and gene-environment interactions. Patients were followed up for a median of 55.7 months. Results: MYH11 rs115364997 G carriers (OR = 1.629; 95%CI: 1.077-2.462, P = 0.020) or TGFBR1 rs1626340 A carriers (OR = 1.500; 95CI: 1.032-2.181, P = 0.033) had a higher risk of DeBakey type Ⅲ AD. MYH11, TGFB1, TGFBR1, and environment interactions are contribute to DeBakey type Ⅲ AD risk (CVC=10/10, P = 0.001). Dominant models of MYH11 rs115364997 AG+GG genotype (HR = 2.443; 95%CI:1.096-5.445, P = 0.029), TGFB1 rs1800469 AG+GG (HR = 2.303; 95%CI:1.069-4.96, P = 0.033) were associated with a higher risk of mortality in DeBakey type III AD. TGFB1 rs1800469 dominant model AG+GG genotype was associated with a higher risk of recurrence of chest pain in DeBakey type III AD (HR = 1.566; 95%CI: 1.018-2.378, P = 0.041). Conclusions: This study indicated that variations of MYH11 rs115364997 and TGFBR1 rs1626340 are associated with genetic predisposition of DeBakey type III AD. G carriers of MYH11 rs115364997 or TGFB1 rs1800469 may be the poor prognostic indicators of mortality and recurrent chest pain in DeBakey type III AD. The interactions of gene-gene and gene-environment are associated with the risk of DeBakey type III AD.