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

Mamm Genome. 2022 Sep;33(3):555-563. doi: 10.1007/s00335-021-09929-6. Epub 2021 Nov 2.

Abstract

To investigate the association of myosin heavy chain protein 11 (MYH11) and transforming growth factor β signaling-related gene polymorphisms with the susceptibility of DeBakey type III aortic dissection (AD) and its clinical outcomes. Four single-nucleotide polymorphism (SNPs) (MYH11 rs115364997, rs117593370, TGFB1 rs1800469, and TGFBR1 rs1626340) were analyzed in patients with DeBakey III AD (173) and healthy participants (335). Gene-gene and gene-environment interactions were evaluated using generalized multifactor dimensionality reduction. The patients were followed up for a median of 55.7 months. MYH11 rs115364997 G or TGFBR1 rs1626340 A carriers had an increased risk of DeBakey type III AD. MYH11, TGFB1, TGFBR1, and environment interactions contributed to the risk of DeBakey type III AD (cross-validation consistency = 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 an increased risk of mortality in DeBakey type III AD. The dominant model of TGFB1 rs1800469 AG + GG genotype was associated with an increased risk of recurrence of chest pain in DeBakey type III AD (HR = 1.566; 95%CI: 1.018-2.378, P = 0.041). In conclusions, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aortic Dissection* / genetics
  • Aortic Dissection* / pathology
  • Chest Pain / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Myosin Heavy Chains / genetics*
  • Myosin Heavy Chains / metabolism
  • Polymorphism, Single Nucleotide*
  • Receptor, Transforming Growth Factor-beta Type I / genetics*
  • Receptor, Transforming Growth Factor-beta Type I / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta1 / genetics*
  • Transforming Growth Factor beta1 / metabolism

Substances

  • MYH11 protein, human
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Receptor, Transforming Growth Factor-beta Type I
  • TGFBR1 protein, human
  • Myosin Heavy Chains