■观察到肉毒杆菌毒素A(BoNT-A)治疗原发性Meige综合征的临床疗效存在个体差异。我们的研究旨在探讨BoNT-A治疗原发性Meige综合征的临床疗效与SNAP25,SV2C和ST3GAL2的变体之间的潜在关联,这些变体涉及BoNT-A的体内易位。
■纳入使用BoNT-A治疗的原发性Meige综合征患者。通过运动症状的最大改善率和疗效持续时间来评估临床疗效。通过Sanger测序获得SNAP25、SV2C和ST3GAL2的变体。另一个被诊断为原发性宫颈肌张力障碍的队列也被纳入复制阶段。
■在104例原发性Meige综合征患者中,80例(76.9%)疗效较好(运动症状改善率最大≥30%),24例(23.1%)有较差(运动症状的最年夜改良率<30%)。至于疗效的持续时间,52例患者(50.0%)的疗效持续时间长(≥4个月),52例(50.0%)有一个短(<4个月)。就原发性Meige综合征而言,SNAP25rs6104571与运动症状的最大改善率相关(基因型:P=0.02,OR=0.26;等位基因:P=0.013,OR=0.29),SV2Crs31244与疗效持续时间相关(基因型:P=0.024,OR=0.13;等位基因:P=0.012,OR=0.13)。此外,我们还进行了变异体与BoNT-A相关不良反应之间的关联分析.虽然,SV2Crs31244等位基因与BoNT-A相关不良反应无统计学差异,有一定的趋势(P=0.077,OR=2.56)。在复制阶段,我们纳入了39例原发性宫颈肌张力障碍患者,以进一步扩大样本量.在39例原发性宫颈肌张力障碍患者中,25例(64.1%)疗效较好(运动症状最大改善率≥50%),14例(35.9%)疗效较差(运动症状最大改善率<50%)。至于疗效的持续时间,32例患者(82.1%)的疗效持续时间长(≥6个月),和7(17.9%)短(<6个月)。合并原发性Meige综合征和原发性宫颈肌张力障碍,SV2Crs31244仍然与疗效持续时间相关(基因型:P=0.002,OR=0。23;等位基因:P=0.001,OR=0。25).
■在我们的研究中,SNAP25rs6104571与使用BoNT-A治疗的原发性Meige综合征患者的运动症状的最大改善率相关,携带该变体的患者运动症状改善率较低。SV2Crs31244与使用BoNT-A治疗的原发性Meige综合征患者的治疗持续时间相关,而携带该变体的患者的治疗持续时间较短。携带SV2Crs31244G等位基因的原发性Meige综合征患者发生BoNT-A相关不良反应的可能性增加。涉及39例原发性宫颈肌张力障碍,结果进一步证实,SV2Crs31244与治疗持续时间相关,携带该变异体的患者的治疗持续时间较短.
UNASSIGNED: Individual differences were observed in the clinical efficacy of Botulinum toxin A (BoNT-A) in the treatment of the primary Meige syndrome. Our study aimed to explore the potential associations between the clinical efficacy of BoNT-A in the treatment of the primary Meige syndrome and variants of SNAP25, SV2C and ST3GAL2, which are involving in the translocation of the BoNT-A in vivo.
UNASSIGNED: Patients with the primary Meige syndrome treated with BoNT-A were enrolled. Clinical efficacy was evaluated by the maximum improvement rate of motor symptoms and the duration of efficacy. Variants of SNAP25, SV2C and ST3GAL2 were obtained by Sanger sequencing. Another cohort diagnosed with primary cervical dystonia was also enrolled in the replication stage.
UNASSIGNED: Among the 104 primary Meige syndrome patients, 80 patients (76.9%) had a good efficacy (the maximum improvement rate of motor symptoms ≥30%) and 24 (23. 1%) had a poor (the maximum improvement rate of motor symptoms <30%). As to the duration of efficacy, 52 patients (50.0%) had a long duration of efficacy (≥4 months), and 52 (50.0%) had a short (<4 months). In terms of primary Meige syndrome, SNAP25 rs6104571 was found associating with the maximum improvement rate of motor symptoms (Genotype: P = 0.02, OR = 0.26; Allele: P = 0.013, OR = 0.29), and SV2C rs31244 was found associating with the duration of efficacy (Genotype: P = 0.024, OR = 0.13; Allele: P = 0.012, OR = 0.13). Besides, we also conducted the association analyses between the variants and BoNT-A-related adverse reactions. Although, there was no statistical difference between the allele of SV2C rs31244 and BoNT-A-related adverse reactions, there was a trend (P = 0.077, OR = 2.56). In the replication stage, we included 39 patients with primary cervical dystonia to further expanding the samples\' size. Among the 39 primary cervical dystonia patients, 25 patients (64.1%) had a good efficacy (the maximum improvement rate of motor symptoms ≥50%) and 14 (35.9%) had a poor (the maximum improvement rate of motor symptoms <50%). As to the duration of efficacy, 32 patients (82.1%) had a long duration of efficacy (≥6 months), and 7 (17.9%) had a short (<6 months). Integrating primary Meige syndrome and primary cervical dystonia, SV2C rs31244 was still found associating with the duration of efficacy (Genotype: P = 0.002, OR = 0. 23; Allele: P = 0.001, OR = 0. 25).
UNASSIGNED: In our study, SNAP25 rs6104571 was associated with the maximum improvement rate of motor symptoms in patients with primary Meige syndrome treated with BoNT-A, and patients carrying this variant had a lower improvement rate of motor symptoms. SV2C rs31244 was associated with duration of treatment in patients with primary Meige syndrome treated with BoNT-A and patients carrying this variant had a shorter duration of treatment. Patients with primary Meige syndrome carrying SV2C rs31244 G allele have an increase likelihood of BoNT-A-related adverse reactions. Involving 39 patients with primary cervical dystonia, the results further verify that SV2C rs31244 was associated with duration of treatment and patients carrying this variant had a shorter duration of treatment.