Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Int J Mol Sci. 2024 Feb 14;25(4):2286. doi: 10.3390/ijms25042286.
Parkinson's disease (PD) is a common neurodegenerative disorder with a prolonged prodromal phase. Higher urinary bis(monoacylglycerol)phosphate (BMP) levels associate with LRRK2 (leucine-rich repeat kinase 2) and GBA1 (glucocerebrosidase) mutations, and are considered as potential noninvasive biomarkers for predicting those mutations and PD progression. However, their reliability has been questioned, with inadequately investigated genetics, cohorts, and population. In this study, multiple statistical hypothesis tests were employed on urinary BMP levels and sequences of 90 PD-risk single nucleotide polymorphisms (SNPs) from Parkinson's Progression Markers Institution (PPMI) participants. Those SNPs were categorized into four groups based on their impact on BMP levels in various cohorts. Variants rs34637584 and rs34637584 (LRRK2 G2019S) were identified as the most relevant on increasing urinary BMP levels in the PD cohort. Meanwhile, rs76763715 (GBA1) was the primary factor elevating BMP levels in the prodromal cohort compared to its T/C and C/C variants (N370S) and the PD cohort. Proteomics analysis indicated the changed transport pathways may be the reasons for elevated BMP levels in prodromal patients. Our findings demonstrated that higher urinary BMP levels alone were not reliable biomarkers for PD progression or gene mutations but might serve as supplementary indicators for early diagnosis and treatment.
帕金森病（PD）是一种常见的神经退行性疾病，具有较长的前驱期。较高的尿双（单酰基甘油）磷酸盐（BMP）水平与 LRRK2（富含亮氨酸重复激酶 2）和 GBA1（葡萄糖脑苷脂酶）突变相关，被认为是预测这些突变和 PD 进展的潜在非侵入性生物标志物。然而，它们的可靠性受到质疑，因为遗传、队列和人群的研究不够充分。在这项研究中，对来自帕金森病进展标志物研究所（PPMI）参与者的 90 个 PD 风险单核苷酸多态性（SNP）的尿 BMP 水平和序列进行了多次统计假设检验。这些 SNP 根据它们在不同队列中对 BMP 水平的影响分为四组。变体 rs34637584 和 rs34637584（LRRK2 G2019S）被确定为在 PD 队列中增加尿 BMP 水平的最相关变体。同时，与 T/C 和 C/C 变体（N370S）和 PD 队列相比，rs76763715（GBA1）是前驱期队列中升高 BMP 水平的主要因素。蛋白质组学分析表明，改变的运输途径可能是前驱期患者 BMP 水平升高的原因。我们的研究结果表明，单独较高的尿 BMP 水平不是 PD 进展或基因突变的可靠生物标志物，但可能作为早期诊断和治疗的补充指标。
