当前位置: X-MOL 学术Neurotherapeutics › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
BDNF rs6265 Variant Alters Outcomes with Levodopa in Early-Stage Parkinson’s Disease
Neurotherapeutics ( IF 5.7 ) Pub Date : 2020-11-19 , DOI: 10.1007/s13311-020-00965-9
D Luke Fischer 1 , Peggy Auinger 2 , John L Goudreau 3 , Allyson Cole-Strauss 1 , Karl Kieburtz 2 , Jordan J Elm 4 , Mallory L Hacker 5 , P David Charles 5 , Jack W Lipton 1, 6 , Barbara A Pickut 1, 6 , Caryl E Sortwell 1, 6
Affiliation  

Disease outcomes are heterogeneous in Parkinson’s disease and may be predicted by gene variants. This study investigated if the BDNF rs6265 single nucleotide polymorphism (SNP) is associated with differential outcomes with specific pharmacotherapy treatment strategies in the “NIH Exploratory Trials in PD Long-term Study 1” (NET-PD LS-1, n = 540). DNA samples were genotyped for the rs6265 SNP and others (rs11030094, rs10501087, rs1491850, rs908867, and rs1157659). The primary measures were the Unified Parkinson’s Disease Rating Scale (UPDRS) and its motor component (UPDRS-III). Groups were divided by genotype and treatment regimen (levodopa monotherapy vs levodopa with other medications vs no levodopa). T allele carriers were associated with worse UPDRS outcomes compared to C/C subjects when treated with levodopa monotherapy (+ 6 points, p = 0.02) and to T allele carriers treated with no levodopa treatment strategies (UPDRS: + 8 points, p = 0.01; UPDRS-III: + 6 points, p = 0.01). Similar effects of worse outcomes associated with levodopa monotherapy were observed in the BDNF rs11030094, rs10501087, and rs1491850 SNPs. This study suggests the levodopa monotherapy strategy is associated with worse disease outcomes in BDNF rs6265 T carriers. Pending prospective validation, BDNF variants may be precision medicine factors to consider for symptomatic treatment decisions for early-stage PD patients.



中文翻译:

BDNF rs6265 变体改变左旋多巴治疗早期帕金森病的结果

帕金森病的疾病结果是异质的,可以通过基因变异来预测。本研究调查了BDNF rs6265 单核苷酸多态性 (SNP) 是否与“NIH PD 长期研究中的探索性试验 1”(NET-PD LS-1,n  = 540)中特定药物治疗策略的不同结果相关。针对 rs6265 SNP 和其他(rs11030094、rs10501087、rs1491850、rs908867 和 rs1157659)对 DNA 样本进行基因分型。主要措施是统一帕金森病评定量表 (UPDRS) 及其运动成分 (UPDRS-III)。根据基因型和治疗方案(左旋多巴单药治疗vs左旋多巴联合其他药物治疗vs没有左旋多巴)。与接受左旋多巴单药治疗(+ 6 分,p  = 0.02)和未接受左旋多巴治疗策略治疗的 T 等位基因携带者(UPDRS:+ 8 分,p  = 0.01 )相比,T 等位基因携带者与更差的 UPDRS 结果相关;UPDRS-III:+ 6 分,p  = 0.01)。在BDNF rs11030094、rs10501087 和 rs1491850 SNP中观察到与左旋多巴单药治疗相关的较差结果的类似影响。这项研究表明,左旋多巴单药治疗策略与BDNF rs6265 T 携带者的较差疾病结果相关。等待前瞻性验证,BDNF 变异可能是早期 PD 患者对症治疗决策要考虑的精准医学因素。

更新日期:2020-11-21
down
wechat
bug