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Abstract：
Background Differences in the clinical course of heritable thoracic aortic disease based on the disease-causing gene have not been fully evaluated. To clarify the clinical relevance of causative genes in heritable thoracic aortic disease, we assessed the clinical course of patients categorized based on genetic diagnosis. Methods and Results We investigated cardiovascular events and mortality in 518 genetically diagnosed patients in 4 groups: Group 1, FBN1 (n=344); Group 2, TGFBR1, TGFBR2, SMAD3, or TGFB2 (n=74); Group 3, COL3A1 (n=60); and Group 4, ACTA2 or MYH11 (n=40). The median age at the first cardiovascular event ranged from 30.0 to 35.5 years (P=0.36). Patients with gene variants related to transforming growth factor-β signaling had a significantly higher rate of subsequent events than those with FBN1 variants (adjusted hazard ratio, 2.33 [95% CI, 1.60-3.38]; P<0.001). Regarding the incidence of aortic dissection, there were no significant differences among the 4 groups in male patients (36.3%, 34.3%, 21.4%, and 54.2%, respectively; P=0.06). Female patients with COL3A1 variants had a significantly lower incidence than female patients in the other 3 groups (34.2%, 59.0%, 3.1%, and 43.8%, respectively; P<0.001). Conclusions Gene variants related to transforming growth factor-β signaling are associated with a higher incidence of subsequent cardiovascular events than FBN1 variants. COL3A1 variants might be related to a lower incidence of aortic dissection than other gene variants in women only. Identifying the genetic background of patients with heritable thoracic aortic disease is important for determining appropriate treatment.
摘要：
背景基于致病基因的遗传性胸主动脉疾病的临床病程差异尚未得到充分评估。阐明遗传性胸主动脉疾病致病基因的临床相关性，我们评估了根据基因诊断分类的患者的临床病程.方法和结果我们调查了518例遗传诊断患者的心血管事件和死亡率，分为4组：第1组，FBN1（n=344）；第2组，TGFBR1，TGFBR2，SMAD3或TGFB2（n=74）；第3组，COL3A1（n=60）；第4组，ACTA2或MYH11（n=40）。首次心血管事件的中位年龄为30.0至35.5岁（P=0.36）。具有与转化生长因子-β信号相关的基因变异的患者的后续事件发生率明显高于具有FBN1变异的患者（调整后的风险比，2.33[95%CI，1.60-3.38]；P<0.001）。关于主动脉夹层的发病率，男性患者的4组之间没有显着差异（36.3％，34.3%,21.4%,54.2%，分别为；P=0.06)。COL3A1变异的女性患者在其他3组中的发病率明显低于女性患者(34.2%,59.0%,3.1%,和43.8%，分别；P<0.001)。结论与转化生长因子-β信号相关的基因变异与随后心血管事件的发生率高于FBN1变异。仅在女性中，COL3A1变异可能与主动脉夹层的发生率低于其他基因变异有关。确定遗传性胸主动脉疾病患者的遗传背景对于确定适当的治疗方法很重要。
