SMPD1 variants in Chinese Han patients with sporadic Parkinson's disease.
A founder mutation, p.L302P, in sphingomyelin phosphodiesterase 1, acid lysosomal (SMPD1), causing Niemann-Pick disease, a recessive lysosomal storage disorder, was reported to be associated with increased risk of Parkinson's disease (PD) in Ashkenazi Jewish population. Several other studies about the association between SMPD1 variants and PD were performed afterward in other populations. However, the results on the role of SMPD1 mutations for PD have been conflicting. This study aimed to investigate the role of mutations in SMPD1 in Chinese PD patients.



We sequenced all the exons of this gene in 512 Chinese Han cases with sporadic Parkinson's disease and 495 matched healthy control subjects.



We identified Leu-Ala (Val) repeat variants and six known single nucleotide variants (p.A36V, p.D212D, p.P332R, p.G508R, p.P533L, p.T544T) in SMPD1 in both patients and normal controls. Case-control analysis showed the association between Leu-Ala (Val) repeat variants in SMPD1and Chinese Han patients with PD (χ2= 8.771, p = 0.012), and the allele with less than seven LeuAla (Val) repeats may increase the risk of PD (p = 0.010).



We identified association between Leu-Ala (Val) repeat variants in SMPD1 and Chinese Han patients with sporadic Parkinson's disease. Our results provide further support for the role of lysosomal pathways in PD development.
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Cheng-Yuan
CY
Mao
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Jing
J
Yang
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Hui
H
Wang
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Shu-Yu
SY
Zhang
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Zhi-Hua
ZH
Yang
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Hai-Yang
HY
Luo
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Fang
F
Li
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Mengmeng
M
Shi
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
Yu-Tao
YT
Liu
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, 20892, MD, USA.
Zheng-Ping
ZP
Zhuang
International Joint Research Laboratory for Cell and Gene Therapy of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou, 450000, Henan, China.
Pan
P
Du
International Joint Research Laboratory for Cell and Gene Therapy of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou, 450000, Henan, China.
Yao-He
YH
Wang
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China. Electronic address: shichanghe@gmail.com.
Chang-He
CH
Shi
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China. Electronic address: xuyuming@zzu.edu.cn.
Yu-Ming
YM
Xu
D000368:Aged; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D016022:Case-Control Studies; D004151:Dipeptides / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics*
D004151:Dipeptides; C470014:leucyl-alanine; C543066:SMPD1 protein, human; D013108:Sphingomyelin Phosphodiesterase
Chinese population; Parkinson's disease; SMPD1; Variant