1. Association of LAG3 genetic variation with an increased risk of PD in Chinese female population.
- Author
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Guo, Wenyuan, Zhou, Miaomiao, Qiu, Jiewen, Lin, Yuwan, Chen, Xiang, Huang, Shuxuan, Mo, Mingshu, Liu, Hanqun, Peng, Guoyou, Zhu, Xiaoqin, and Xu, Pingyi
- Subjects
SINGLE nucleotide polymorphisms ,PARKINSON'S disease ,DOPAMINERGIC neurons ,LINKAGE disequilibrium ,CEREBROSPINAL fluid ,ANTIGENS ,DISEASE susceptibility ,GENETIC polymorphisms ,GENETIC markers ,CASE-control method ,GENOTYPES - Abstract
Background: Emerging evidence suggests that α-synuclein (α-syn) aggregation and intercellular transmission contributes to pathogenesis of Parkinson's disease (PD) and the toxic fibrillary α-syn binds lymphocyte-activation gene 3 (LAG3) receptor that mediates α-syn transmission. The deletion of LAG3 in animal models was shown to limit α-syn spreading and alleviate the pathological changes of dopaminergic neurons and animal behavioral deficits induced by α-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 < 0.0001). Meanwhile, the concentration of α-synuclein in CSF of patients was significantly lower than that of controls (939.9 ± 2900 pg/ml vs 2476 ± 4403 pg/ml, p < 0.0001) and the level of sLAG3 was detected to be positive correlation with that of α-synuclein in the control group (r = 0.597, p = 0.0042), but not in PD group (r = 0.111, p = 0.408).Conclusion: In summary, our data suggested that LAG3 SNPs increase the PD risk of Chinese female population and the sLAG3 may be a potential biomarker predicted for PD development. [ABSTRACT FROM AUTHOR]- Published
- 2019
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