在SMAD3病原性变异寄托个体中的性二态
Julie Richer1,2, Joe Davis Velchev3, Sharan Goobie4
1Department of Medical Genetics, Children's Hospital of Eastern Ontario Regional Genetics Program, Ottawa, Ontario, Canada juricher@cheo.on.ca.
Journal of medical genetics
|January 2, 2025
概括
患有SMAD3变异的女性表现出较高的血管疾病不穿透率,这意味着与男性相比,她们不太可能发展动脉瘤或剖析. 这种透率的差异影响了我们如何理解和诊断SMAD3变异携带者的血管疾病.
科学领域:
- 遗传学和心血管医学
- 血管生物学和疾病机制
背景情况:
- SMAD3中的致病变体与动脉瘤和动脉树的剖析风险有关.
- 之前的研究表明胸前动脉动脉瘤和剖析的性别差异,促使对SMAD3相关的血管事件进行调查.
研究的目的:
- 在携带致病性SMAD3变体的患者中调查血管事件中的性二态.
- 确定SMAD3变异携带者的血管病理的表现和位置是否存在性别特异.
主要方法:
- 分析了两个大型血统 (84个个体),其中SMAD3中具有致病性误解变异,影响p.Arg287.
- 排除40岁以下没有血管损伤的个人;按性别分类,血管损伤存在/不存在以及位置 (大动脉根/上升大动脉损伤).
- 从文献 (2011-2023) 中补充178名SMAD3患者的家族队列,进行综合分析.
主要成果:
- 女性 (37%) 没有表现出血管干扰,而不是所有的男性 (n=23) 在血统 (p=0.001).
- 男性表现出较高的血管并发症风险 (p=0.037),与女性相比,大动脉根/上升大动脉参与有显著差异 (4%对32%,p=0.034).
- 在综合队列 (220名患者) 中,男性的比例过高 (p<0.001),女性的甲状腺根/上升性甲状腺病理不透率较高 (p=0.028).
结论:
- 血管病理的非透性在携带SMAD3变异的女性中更为普遍.
- 风险女性的正常心声回声可能无法完全排除其他动脉部位的血管病变风险.
- 在女性中较高的非透率有助于确定偏差,导致SMAD3出版文献中男性的过度代表性.
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