Objective: Sequencing of Parkinson Disease（PD) genes were used in our research in order to study the polymorphism of PD related genes of Chinese Han people.

Background: The pathogenesis of PD is still unclear. Genetic factor of PD pathogenesis is getting extensive attention recently. Sequencing of PD gene polymorphism have been conducted worldwide.

Methods: 297 PD patient were enrolled in our research, including 41 early-onset PD patients, 235 late-onset PD patients and 21 familial PD patients. DNA were extracted from the peripheral blood of these patients. PD related gene target sequencing were done in 195 patients, whole exome sequencing were conducted in 102 patients. Further,we compared the variants with 1000 Genome Project, Exome Aggregation Consortium, ACMG and dpSNP database, The variants with a minor allele frequency less than 0.005 were verified by Sanger sequencing.

Results: In early-onset and familial PD patients, 19 patients were found variations(30.6%). Five patients were found variation in GBA(L216I,N140K,L396R,L137R)(8.1%), one patient was found variants in LRRK2(M100T)(1.6%), nine patients were tested PARKIN(Q63X, Shear mutation, W74X,G135R,G284R) variation (14.5%), three patients were found MAPT(L48V, E45V, P523A)variation(4.8%). In late-onset PD patients, 121 patients (79.6%) were detected variations, 89 patients (58.6%) had LRRK2 variations(G2385R, R1628P, R1325Q, L153W, C925Y, S1007T, P755L, A419V, G2019S, N2308D, S722N, R792K, R981K, R1320S, N2313S, A459S, S2350I, V1447M, R1677S), 14 patients (9.2%) had GBA variations(S223G, q265X, N227K, G643C, D361H, S77R, Q32K, G39V,R209Q, A128P, G151R, N140S), six patients (3.9%)were found PARKIN variation (G135R, A142T, R253H, H312fs). There was each one patient (0.7%) was found MAPT(R5H), SNCA(P117S), VPS35(R54Q) variation and three patients(2.0%) were found PLA2G6 (G266A, D331Y, D331Y), EIF4G1 (V1035A, P435T, R1219Q), three patients were found SYNJ1 (A507V, Q1077R, shear mutation) variations.

Conclusions: LRRK2 variation was most common in Chinese Han PD patients and highly detectable in late-onset PD patients. PARKIN variation was found a higher percentage in early-onset PD patients. Other genes were found no significant difference between different groups. We also found some gene polymorphism sites which have never been reported before, but further research were needed before we found the significance of these sites toward PD pathogenesis.

References: 1. Kalia LV, Lang AE. Parkinson’s disease. Lancet Lond. Engl. 2015;386:896–912. 2. Tan EK, Peng R, Teo YY, et al. Multiple LRRK2 variants modulate risk of Parkinson disease: a Chinese multicenter study. Hum Mutat 2010;31:561-568.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/analysis-of-gene-polymorphisms-of-parkinsons-disease-in-han-chinese-population/