Association of LAG3 genetic variation with an increased risk of PD in Chinese female population.

ABSTRACT: BACKGROUND:Emerging evidence suggests that ?-synuclein (?-syn) aggregation and intercellular transmission contributes to pathogenesis of Parkinson's disease (PD) and the toxic fibrillary ?-syn binds lymphocyte-activation gene 3 (LAG3) receptor that mediates ?-syn transmission. The deletion of LAG3 in animal models was shown to limit ?-syn spreading and alleviate the pathological changes of dopaminergic neurons and animal behavioral deficits induced by ?-syn aggregation. However, little is known about the genetic association of LAG3 variation with human PD development. OBJECTIVE:Here we investigated LAG3 single nucleotide polymorphisms (SNPs) and examined the levels of soluble LAG3 (sLAG3) of CSF and serum from Chinese PD patients. METHODS:We enrolled 646 PD patients and 536 healthy controls to conduct a case-control study. All the participants were genotyped using Sequenom iPLEX Assay and the partial cerebrospinal fluid (CSF) and serum samples were assessed by Meso Scale Discovery electrochemiluminescence (MSD-ECL) immunoassay to measure sLAG3 concentration. RESULTS:As a result, distributions of rs1922452-AA (1.975, 95% confidence interval (CI) 1.311-2.888, p?=?0.001) and rs951818-CC (OR?=?2.03, 95% CI 1.369-3.010, p?=?0.001) genotype frequencies were found higher in the female PD patients than controls, respectively, and a strong linkage disequilibrium (LD) was calculated on the variants. The level of sLAG3 in CSF of PD patients was found to significantly differ from that of controls (51.56?±?15.05?pg/ml vs 88.49?±?62.96?pg/ml, p?

SUBMITTER: Guo W 

PROVIDER: S-EPMC6918662 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature