Association of gene polymorphisms in FBN1 and TGF-β signaling with the susceptibility and prognostic outcomes of Stanford type B aortic dissection

BMC Med Genomics. 2022 Mar 20;15(1):65. doi: 10.1186/s12920-022-01213-z.

Abstract

Background: This study is aimed at investigating the association of Fibrillin-1 (FBN1) and transforming growth factor β (TGF-β) signaling-related gene polymorphisms with the susceptibility of Stanford type B aortic dissection (AD) and its clinical prognostic outcomes.

Methods: Five single-nucleotide polymorphism (SNPs) (FBN1rs 145233125, rs201170905, rs11070646, TGFB1rs1800469, and TGFB2rs900) were analyzed in patients with Stanford type B AD (164) and healthy controls (317). Gene-gene and gene-environment interactions were assessed by generalized multifactor dimensionality reduction. A 4-year follow-up was performed for all AD patients.

Results: G carriers of FBN1 rs201170905 and TGFB1 rs1800469 have an increased risk of Stanford type B AD. The interaction of FBN1, TGFB1, TGFB2 and environmental promoted to the increased risk of type B AD (cross-validation consistency = 10/10, P = 0.001). Dominant models of FBN1rs145233125 TC + CC genotype (P = 0.028), FBN1 rs201170905 AG + GG (P = 0.047) and TGFB1 rs1800469 AG + GG (P = 0.052) were associated with an increased risk of death of Stanford type B AD. The recessive model of FBN1 rs145233125 CC genotype (P < 0.001), FBN1rs201170905 GG (P < 0.001), TGFB1 rs1800469 AG + GG genotype (P = 0.011) was associated with an increased risk of recurrence of chest pain in Stanford type B AD.

Conclusions: The interactions of gene-gene and gene-environment are related with the risk of Stanford type B AD. C carriers of rs145233125, G carriers of rs201170905 and G carriers of rs1800469 may be the poor clinical outcome indicators of mortality and recurrent chest pain in Stanford type B AD.

Keywords: Aortic dissection; FBN1; GMDR; SNP; TGFB1; TGFB2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aortic Dissection* / genetics
  • Chest Pain
  • Fibrillin-1 / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Transforming Growth Factor beta* / genetics

Substances

  • FBN1 protein, human
  • Fibrillin-1
  • Transforming Growth Factor beta