Association of polymorphisms in FBN1, MYH11, and TGF-β signaling-related genes with susceptibility of sporadic thoracic aortic aneurysm and dissection in the Zhejiang Han population

The genetic basis of sporadic thoracic aortic aneurysm and dissection (sTAAD) has not been fully explored. Thus, we investigated the association between polymorphisms in myosin heavy chain 11 ( MYH11 ), fibrillin-1 ( FBN1 ), and transforming growth factor β (TGF-β) signaling-related genes with sTAAD susceptibility. Herein, 122 sTAAD patients and 98 healthy individuals were recruited, and 10 single nucleotide polymorphisms (SNPs) were selected and analyzed ( FBN1 rs10519177, rs1036477, rs2118181, MYH11 rs115364997, rs117593370, TGF β 1 rs1800469, TGF β 2 rs900, TGF β R2 rs764522, rs1036095, and rs6785385). Moreover, multiple logistic regression analysis was used to evaluate gene-environment interactions. TGF β R2 rs1036095, FBN 1 rs1036477, and FBN1 rs2118181 were identified as factors of increased risk of sTAAD. TGF β R2 rs1036095 dominant model CC+CG genotype (P=0.004), FBN1 rs1036477 recessive model AA genotype(P=0.009), and FBN1 rs2118181 dominant model CC+CT genotype(P=0.009) were correlated to an increased death rate in sTAAD patients. Furthermore, TGF β R2 rs6785385, FBN1 rs10519177, FBN1 rs1036477, and FBN1 rs2118181 were discovered to be bound up with an increased risk of sTAAD in men, whereas TGF β R2 rs1036095 was correlated to an increased risk of death from women sTAAD. Gene-environment interactions indicated TGF β R2 rs1036095 dominant model (CC+CG)/GG to be a higher risk factor for sTAAD (OR=3.255,95%CI 1.324–8.000, P=0.01). Moreover, variations of TGF β R2 rs1036095, FBN1 rs1036477, and FBN1 rs2118181 were identified to be associated with sTAAD in the Zhejiang Han population. Furthermore, TGF β R2 rs1036095 might be a prognostic indicator of mortality in sTAAD in women. Gene-environment interactions were associated with the risk of sTAAD.