Huang Lifang, Liu Mao, Tang Jiahui, Gong Zhenxiang, Li Zehui, Yang Yuan, Zhang Min
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Neurology, SUNY Downstate Health Sciences University, Brooklyn, NY, United States.
Front Neurosci. 2024 Sep 3;18:1397991. doi: 10.3389/fnins.2024.1397991. eCollection 2024.
The aldehyde dehydrogenase 2 () rs671 (A) allele has been implicated in neurodegeneration, potentially through oxidative and inflammatory pathways. The study aims to investigate the effects of the rs671 (A) allele and high sensitivity C-reactive protein (hs-CRP) on the clinical phenotypes of amyotrophic lateral sclerosis (ALS) in male and female patients.
Clinical data and rs671 genotype of 143 ALS patients, including 85 males and 58 females, were collected from January 2018 to December 2022. All patients underwent assessment using the Chinese version of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Complete blood count and metabolic profiles were measured. Clinical and laboratory parameters were compared between carriers and non-carriers of the rs671 (A) allele in males and females, respectively. The significant parameters and rs671 (A) Allele were included in multivariate linear regression models to identify potential contributors to motor and cognitive impairment. Mediation analysis was employed to evaluate any mediation effects.
Male patients carrying rs671 (A) allele exhibited higher levels of hs-CRP than non-carriers (1.70 mg/L vs. 0.50 mg/L, = 0.006). The rs671 (A) allele was identified as an independent risk factor for faster disease progression only in male patients (β = 0.274, 95% CI = 0.048-0.499, = 0.018). The effect of the rs671 (A) allele on the executive function in male patients was fully mediated by hs-CRP (Indirect effect = -1.790, 95% CI = -4.555--0.225). No effects of the rs671 (A) allele or hs-CRP were observed in female ALS patients. The effects of the rs671 (A) allele and the mediating role of hs-CRP in male patients remained significant in the sensitivity analyses.
The rs671 (A) allele contributed to faster disease progression and hs-CRP mediated cognitive impairment in male ALS patients.
醛脱氢酶2（）rs671（A）等位基因可能通过氧化和炎症途径与神经退行性变有关。本研究旨在探讨rs671（A）等位基因和高敏C反应蛋白（hs-CRP）对男性和女性肌萎缩侧索硬化症（ALS）临床表型的影响。
收集2018年1月至2022年12月期间143例ALS患者的临床资料和rs671基因型，其中男性85例，女性58例。所有患者均使用中文版的爱丁堡认知和行为性ALS筛查量表（ECAS）进行评估。检测血常规和代谢指标。分别比较男性和女性中rs671（A）等位基因携带者和非携带者的临床和实验室参数。将显著参数和rs671（A）等位基因纳入多元线性回归模型，以确定运动和认知障碍的潜在影响因素。采用中介分析评估任何中介效应。
携带rs671（A）等位基因的男性患者hs-CRP水平高于非携带者（1.70 mg/L对0.50 mg/L，P = 0.006）。仅在男性患者中，rs671（A）等位基因被确定为疾病进展更快的独立危险因素（β = 0.274，95%CI = 0.048 - 0.499，P = 0.018）。rs671（A）等位基因对男性患者执行功能的影响完全由hs-CRP介导（间接效应 = -1.790，95%CI = -4.555 - -0.225）。在女性ALS患者中未观察到rs671（A）等位基因或hs-CRP的影响。在敏感性分析中，rs671（A）等位基因的影响以及hs-CRP在男性患者中的中介作用仍然显著。
rs671（A）等位基因导致男性ALS患者疾病进展更快，且hs-CRP介导认知障碍。
