Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, CHINA.
Department of Radiology, Huashan Hospital, Fudan University, Shanghai, CHINA.
Med Sci Sports Exerc. 2023 Jun 1;55(6):1114-1120. doi: 10.1249/MSS.0000000000003134. Epub 2023 Feb 9.
It has been hypothesized that the corticospinal tract (CST) is involved in the neural origins underlying muscular deficits after an ankle sprain. Microstructural differences in the CST have been reported in patients with and without a history of ankle sprain, but the causal links between the CST and the injuries have not been verified. This study aimed to explore whether genetically predisposed ankle sprains would impair the integrity and organization of CST neurites, manifesting as reduced fractional anisotropy (FA) and increased orientation dispersion index (ODI).
Single-nucleotide polymorphisms (SNP) associated with ankle sprains were identified from genome-wide association studies (GWAS) in FinnGen based on hospital discharge records (7223 cases and 245,598 controls). Outcome statistics for CST microstructures were collected from the GWAS from diffusion-weighted-imaging outcomes in the UK Biobank (33,224 participants). Random-effect, inverse-variance weighted Mendelian randomization was used as the primary method.
Eighteen SNP were selected as forming possible causal links between ankle sprains and CST structure; F value ranged from 755 to 1026. Ankle sprains were associated with a reduction in the FA of the right CST ( β = -0.033, P = 0.0439), whereas no significant effects were observed on the left side ( β = -0.029, 0.004; P = 0.0748). Ankle sprains significantly increased the ODI of the left CST ( β = 0.053, P = 0.0036) and the right CST ( β = 0.038, P = 0.0259). No significant pleiotropy or heterogeneity was observed in the analyses.
A genetic predisposition to ankle sprains can lead to maladaptive neuroplasticity of the CST, manifesting as abnormally organized neurites.
据推测，皮质脊髓束（CST）参与了踝关节扭伤后肌肉功能障碍的神经起源。已有研究报道，踝关节扭伤患者和无踝关节扭伤病史患者的 CST 存在微观结构差异，但 CST 与损伤之间的因果关系尚未得到验证。本研究旨在探讨遗传性踝关节扭伤是否会损害 CST 神经突的完整性和组织，表现为各向异性分数（FA）降低和方向分散指数（ODI）升高。
从 FinnGen 基于住院记录的全基因组关联研究（GWAS）中确定与踝关节扭伤相关的单核苷酸多态性（SNP）（7223 例病例和 245598 例对照）。CST 微观结构的结果统计数据来自 UK Biobank 的基于扩散加权成像结果的 GWAS（33224 名参与者）。采用随机效应、逆方差加权孟德尔随机化作为主要方法。
选择了 18 个 SNP 作为踝关节扭伤与 CST 结构之间可能存在因果关系的标志物，F 值范围为 755 至 1026。踝关节扭伤与右侧 CST 的 FA 降低相关（β=-0.033，P=0.0439），而左侧无显著影响（β=-0.029，0.004；P=0.0748）。踝关节扭伤显著增加了左侧 CST（β=0.053，P=0.0036）和右侧 CST（β=0.038，P=0.0259）的 ODI。分析中未观察到明显的异质性或多效性。
遗传性踝关节扭伤可导致 CST 的神经适应性可塑性异常，表现为神经突异常组织化。
