种族对单基因疾病表型的影响:脊髓小脑共济失调3型(P1.8-002)

摘要目的:目的探讨民族对脊髓小脑性共济失调3型(SCA3)表型的影响。

背景:对于各种散发性神经退行性疾病，如阿尔茨海默病、帕金森病和肌萎缩侧索硬化症，种族确实会影响疾病的表型，这是公认的。然而，种族如何影响单基因疾病的临床症状和疾病进展，如脊髓小脑性共济失调3型(SCA3)，研究仍然较少。

设计/方法:我们对257名分子确诊的SCA3患者(66名白种人，43名非裔美国人，148名亚洲人，其中131名中国人和17名亚裔美国人)使用多变量线性和逻辑回归模型来探讨种族对发病年龄(AAO)、共济失调严重程度和非共济失调症状患病率的影响。我们还采用广义估计方程模型来分析种族对共济失调进展的影响。

结果:在调整病理CAG重复数后，我们发现亚洲人的AAO明显晚于白种人(β = 4.75, p = 0.000)和非洲裔美国人(β = 6.64, p = 0.000)。考虑病理CAG重复数和病程，非裔美国人表现出较白种人(β = 3.81, p = 0.004)和亚洲人(β = 4.39, p = 0.001)更严重的共济失调。然而，3个种族间的共济失调进展无显著差异。另一方面，白种人患抑郁症的频率高于非裔美国人(β = 1.23, p = 0.040)。

结论:SCA3患者在不同种族中具有表型变异和不同的疾病进展率，这可能值得临床研究和公共卫生考虑。这些结果突出了种族在单基因神经退行性疾病中的作用。

披露:甘博士没有什么要透露的。菲格罗亚医生没什么可透露的。帕尔曼博士没有什么要透露的。威尔莫特博士没有什么要透露的。戈麦斯医生没有什么要透露的。Schmahmann博士在Ataxion / Cadent、Biohaven Pharmaceuticals和Pfizer担任咨询、科学顾问委员会、演讲或其他活动的个人报酬。鲍尔森没有什么要透露的。shakkotai博士没有什么可透露的。应博士没有什么要透露的。Zesiewicz博士因咨询、担任科学顾问委员会、演讲或其他活动而获得个人报酬。 Dr. Zesiewicz has received research support from Abbive, Biogen, Biohaven, Cavion. Dr. Bushara has nothing to disclose. Dr. Geschwind has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Quest Inc., Advance Medical Inc, Guidepoint Global, Market Plus, Best Doctors, Gerson Lehrman Group, 3MCommunications, Insight Consulting, and Smith & Hennessey LLC. Dr. Geschwind has received research support from Quest Diagnostics. Dr. Xia has nothing to disclose. Dr. Subramony has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acceleron Pharma. Dr. Subramony has received research support from Acceleron, Reata, Takeda, Horizon, and Biohaven. Dr. Ashizawa has nothing to disclose. Dr. Pulst has received personal compensation in an editorial capacity for Wolters Kluwer (Editor: Neurology Genetics). Dr. Pulst has received royalty, license fees, or contractual rights payments from Cedars-Sinai Medical Center. Dr. Wang has nothing to disclose. Dr. Kuo has nothing to disclose.