Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Senen University, Guangzhou, China.
Department of Cardiology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.
Mamm Genome. 2022 Sep;33(3):555-563. doi: 10.1007/s00335-021-09929-6. Epub 2021 Nov 2.
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.
为了研究肌球蛋白重链蛋白 11（MYH11）和转化生长因子β信号相关基因多态性与 DeBakey Ⅲ型主动脉夹层（AD）易感性及其临床结局的关系。在 DeBakey Ⅲ型 AD 患者（173 例）和健康对照者（335 例）中分析了 4 个单核苷酸多态性（SNP）（MYH11 rs115364997、rs117593370、TGFB1 rs1800469 和 TGFBR1 rs1626340）。采用广义多因素降维法评价基因-基因和基因-环境相互作用。对患者进行了中位数为 55.7 个月的随访。MYH11 rs115364997 G 或 TGFBR1 rs1626340 A 携带者患 DeBakey Ⅲ型 AD 的风险增加。MYH11、TGFB1、TGFBR1 和环境相互作用导致 DeBakey Ⅲ型 AD 发病风险增加（交叉验证一致性=10/10，P=0.001）。MYH11 rs115364997 AG+GG 基因型的显性模型（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）与 DeBakey Ⅲ型 AD 患者死亡风险增加相关。TGFB1 rs1800469 AG+GG 基因型的显性模型与 DeBakey Ⅲ型 AD 患者胸痛复发风险增加相关（HR=1.566；95%CI：1.018-2.378，P=0.041）。结论：MYH11 rs115364997 或 TGFB1 rs1800469 的 G 携带者可能是 DeBakey Ⅲ型 AD 患者死亡和胸痛复发的不良预后指标。基因-基因和基因-环境的相互作用与 DeBakey Ⅲ型 AD 的发病风险相关。
