SMPD1 variants in Chinese Han patients with sporadic Parkinson's disease
SMPD1 variants in Chinese Han patients with sporadic Parkinson's disease
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中国汉族散发性帕金森病患者的 SMPD1 变异
DOI：
10.1016/j.parkreldis.2016.10.014
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发表时间：
2017-01-01
影响因子：
4.1
通讯作者：
Xu, Yu-ming
中科院分区：
文献类型：
--
作者：
Mao, Cheng-yuan;Yang, Jing;Xu, Yu-ming
简介：酸性溶酶体鞘磷脂磷酸二酯酶 1 (SMPD1) 中的始祖突变 p.L302P 会导致尼曼-匹克病（一种隐性溶酶体贮积症），据报道与德系犹太人中帕金森病 (PD) 风险增加相关。随后在其他人群中进行了几项关于 SMPD1 变异与 PD 之间关联的研究。然而，关于 SMPD1 突变对 PD 的作用的结果一直相互矛盾。本研究旨在探讨 SMPD1 突变在中国 PD 患者中的作用。方法：我们对 512 名中国汉族散发性帕金森病患者和 495 名匹配的健康对照受试者的该基因的所有外显子进行了测序。结果：我们鉴定了 Leu-Ala (Val) 重复变异和 6 个已知的单核苷酸变异（p.A36V、p.D212D、p.P332R、p.G508R、患者和正常对照中 SMPD1 中的 p.P533L、p.T544T）。病例对照分析显示，SMPD1 中的 Leu-Ala (Val) 重复变异与中国汉族 PD 患者之间存在相关性 (chi(2) = 8.771，p = 0.012），并且少于 7 个 LeuAla (Val) 重复的等位基因可能会增加 PD 风险 (p = 0.010)。结论：我们确定了 SMPD1 中的 Leu-Ala (Val) 重复变异与中国汉族散发性 PD 患者之间的相关性。帕金森病。我们的结果为溶酶体途径在帕金森病发展中的作用提供了进一步的支持。 (C) 2016 Elsevier Ltd. 保留所有权利。
Introduction: 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.Methods: We sequenced all the exons of this gene in 512 Chinese Han cases with sporadic Parkinson's disease and 495 matched healthy control subjects.Results: 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 SMPD1 and Chinese Han patients with PD (chi(2) = 8.771, p = 0.012), and the allele with less than seven LeuAla (Val) repeats may increase the risk of PD (p = 0.010).Conclusion: 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. (C) 2016 Elsevier Ltd. All rights reserved.