Association of MLL3 and TGF-β signaling gene polymorphisms with the susceptibility and prognostic outcomes of Stanford type B aortic dissection : MLL3 with TGF-β signal pathway association with Stanford type B AD

Abstract

Objective: This study aims to investigate the association of lysine methyltransferase 2 C (MLL3) 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. The methods involved investigating the MLL3 (rs10244604, rs6963460, rs1137721), TGFβ1 (rs1800469), TGFβ2 (rs900), TGFR1 (rs1626340) and TGFR2 (rs4522809) gene polymorphisms. Logistic regression was performed to investigate the association between 7 single nucleotide gene polymorphisms (SNPs) and Stanford type B aortic dissection. The GMDR software was used to analyze gene-gene and gene-environment interactions. The odds ratio (OR) with a 95% confidence interval (CI) was employed to evaluate the association of genes and Stanford type B AD risk.

Results: Genotypes and allele distributions in the case and control groups showed significant differences (P < 0.05). Logistic regression has shown that the Stanford Type B AD risk was highest in individuals with the rs1137721 CT genotype (OR = 4.33, 95% CI = 1.51-12.40). Additionally, WBC, drinking, hypertension, triglycerides (TG), and low-density lipoprotein (LDL-C) were independent risk factors for Stanford Type B AD. Logistic regression showed that the Stanford Type B AD risk was highest in individuals with the MLL3 (rs1137721)-TT + CT and TGFβ1 (rs4522809)-AA genotype (OR = 6.72, 95% CI = 1.56-29.84), and lowest in those with the MLL3 (rs1137721)-CC and TGFβ1 (rs4522809)-AA + GG genotype (OR = 4.38, 95% CI = 0.92-20.83). However, the 55-month median long-term follow-up did not show statistical significance.

Conclusion: Carriers of both TT + CT of MLL3 (rs1137721) and AA of TGFβ1 (rs4522809) polymorphisms may be closely related to the development of Stanford type B AD. MLL3 (rs1137721), WBC, and TG/TC were found to be associated with the morbidity of Stanford type B AD. MLL3 (KMT2C) is associated with the TGF-β signaling pathway protein. The risk of Stanford type B AD is related to the interactions of gene-gene and gene-environment.

Keywords: MLL3; Stanford type B AD; TGFβ signal pathway.

Fig. 1

Protein-protein interaction (PPI), lysine methyltransferase 2 C (KMT2C, MLL3) associated with transforming growth factor beta (TGF-β) signal pathway protein

Fig. 2

A: Kaplan–Meier analysis of the overall survival based on lysine methyltransferase 2 C (KMT2C, MLL3) rs1137721 dominant model; B: Kaplan–Meier analysis of the overall survival based on transforming growth factor receptor-2(TGFR2)rs4522809 dominant model;