|
|
帕金森病相关致病基因的多态性及表型特点在中国人群的研究进展
|
Abstract:
帕金森病是一种常见的神经退行性疾病，严重影响了我国数百万中老年人的健康和生活质量。PD的发病机制与环境因素和遗传因素密切相关，具有不同的遗传方式。过去二十年来，PD遗传学的研究取得巨大进步，研究表明不同种族的基因多态性及临床表型存在差异。本文主要对多个PD相关突变基因的多态性及其表型特点在中国人群中的研究做一综述，旨在为PD的不同致病基因携带者提供临床表型及治疗参考。
Parkinson’s disease is a common neurodegenerative disease that seriously affects health and quality of life of millions of middle-aged and elderly people in China. The pathogenesis of Parkin-son’s disease is closely related to environmental factors and genetic factors, and has different ge-netic methods. In the past two decades, research on PD genetics has made great progress. Studies have shown that there are differences in genetic polymorphisms and clinical phenotypes between different races. This article reviews the polymorphisms and phenotypic characteristics of PD-related genes in Chinese population. The aim is to provide clinical phenotypes and treatment references for different pathogenic gene carriers of PD.
| [1] | Tysnes, O.B. and Storstein, A. (2017) Epidemiology of Parkinson’s Disease. Journal of Neural Transmission (Vienna), 124, 901-905. https://doi.org/10.1007/s00702-017-1686-y |
| [2] | Reich, S.G. and Savitt, J.M. (2019) Parkinson’s Disease. Medical Clinics of North America, 103, 337-350.
https://doi.org/10.1016/j.mcna.2018.10.014 |
| [3] | Polo-Morales, A., et al. (2020) Association between Somatization and Nonmotor Symptoms Severity in People with Parkinson Disease. Journal of Geriatric Psychiatry and Neurology, 891988720901787. |
| [4] | Dickson, D.W. (2018) Neuropathology of Parkinson Disease. Parkinsonism & Related Disorders, 46, S30-S33.
https://doi.org/10.1016/j.parkreldis.2017.07.033 |
| [5] | Delamarre, A. and Meissner, W.G. (2017) Epidemiology, Environmental Risk Factors and Genetics of Parkinson’s Disease. La Presse Médicale, 46, 175-181. https://doi.org/10.1016/j.lpm.2017.01.001 |
| [6] | Polymeropoulos, M.H., Lavedan, C., Leroy, E., et al. (1997) Muta-tion in the Alpha-Synuclein Gene Identified in Families with Parkinson’s Disease. Science, 276, 2045-2047. https://doi.org/10.1126/science.276.5321.2045 |
| [7] | Deng, H., Wang, P. and Jankovic, J. (2018) The Genetics of Parkinson Disease. Ageing Research Reviews, 42, 72-85.
https://doi.org/10.1016/j.arr.2017.12.007 |
| [8] | Kim, C.Y. and Alcalay, R.N. (2017) Genetic Forms of Parkinson’s Disease. Seminars in Neurology, 37, 135-146.
https://doi.org/10.1055/s-0037-1601567 |
| [9] | Koros, C., Simitsi, A. and Stefanis, L. (2017) Genetics of Parkinson’s Disease: Genotype-Phenotype Correlations. International Review of Neurobiology, 132, 197-231. https://doi.org/10.1016/bs.irn.2017.01.009 |
| [10] | Seo, S.H., et al. (2020) Replication-Based Rearrangements Are a Common Mechanism for SNCA Duplication in Parkinson’s Disease. Movement Disorders: Official Journal of the Movement Disorder Society. |
| [11] | Ferese, R., Modugno, N., Campopiano, R., et al. (2015) Four Copies of SNCA Re-sponsible for Autosomal Dominant Parkinson’s Disease in Two Italian Siblings. Parkinson’s Disease, 2015, Article ID: 546462.
https://doi.org/10.1155/2015/546462 |
| [12] | Xiong, W.X., Sun, Y.M., Guan, R.Y., et al. (2016) The Heterozygous A53T Mutation in the Alpha-Synuclein Gene in a Chinese Han Patient with Parkinson Disease: Case Report and Lit-erature Review. Journal of Neurology, 263, 1984-1992. https://doi.org/10.1007/s00415-016-8213-1 |
| [13] | Yu, W.J., Cheng, L., Li, N.N., et al. (2015) Interaction between SNCA, LRRK2 and GAK Increases Susceptibility to Parkinson’s Disease in a Chinese Population. eNeurologicalSci, 1, 3-6. https://doi.org/10.1016/j.ensci.2015.08.001 |
| [14] | Li, N.N., Mao, X.Y., Chang, X.L., et al. (2013) SNCA rs356219 Variant Increases Risk of Sporadic Parkinson’s Disease in Ethnic Chinese. American Journal of Medical Genetics Part B Neuropsychiatric Genetics, 162, 452-456.
https://doi.org/10.1002/ajmg.b.32143 |
| [15] | Cheng, L., Wang, L., Li, N.N., et al. (2016) SNCA rs356182 Variant Increases Risk of Sporadic Parkinson’s Disease in Ethnic Chinese. Journal of the Neurological Sciences, 368, 231-234. https://doi.org/10.1016/j.jns.2016.07.032 |
| [16] | Huang, Y., Wang, G., Rowe, D., et al. (2015) SNCA Gene, But Not MAPT, Influences Onset Age of Parkinson’s Disease in Chinese and Australians. BioMed Research International, 2015, Article ID: 135674.
https://doi.org/10.1155/2015/135674 |
| [17] | Chen, W., Kang, W.Y., Chen, S., et al. (2015) Hyposmia Correlates with SNCA Variant and Non-Motor Symptoms in Chinese Patients with Parkinson’s Disease. Parkinsonism & Related Disorders, 21, 610-614.
https://doi.org/10.1016/j.parkreldis.2015.03.021 |
| [18] | Zheng, J., Yang, X., Zhao, Q., et al. (2017) Association between Gene Polymorphism and Depression in Parkinson’s Disease: A Case-Control Study. Journal of the Neurolog-ical Sciences, 375, 231-234.
https://doi.org/10.1016/j.jns.2017.02.001 |
| [19] | Ross, O.A., Soto-Ortolaza, A.I., Heckman, M.G., et al. (2011) As-sociation of LRRK2 Exonic Variants with Susceptibility to Parkinson’s Disease: A Case-Control Study. The Lancet Neurology, 10, 898-908.
https://doi.org/10.1016/S1474-4422(11)70175-2 |
| [20] | Fu, X., Zheng, Y., Hong, H., et al. (2013) LRRK2 G2385R and LRRK2 R1628P Increase Risk of Parkinson’s Disease in a Han Chinese Population from Southern Mainland China. Parkinsonism & Related Disorders, 19, 397-398.
https://doi.org/10.1016/j.parkreldis.2012.08.007 |
| [21] | Xie, C.L., Pan, J.L., Wang, W.W., et al. (2014) The Associ-ation between the LRRK2 G2385R Variant and the Risk of Parkinson’s Disease: A Meta-Analysis Based on 23 Case-Control Studies. Neurological Sciences, 35, 1495-1504.
https://doi.org/10.1007/s10072-014-1878-2 |
| [22] | Zhang, J.R., Jin, H., Li, K., et al. (2018) Genetic Analysis of LRRK2 in Parkinson’s Disease in Han Chinese Population. Neurobiology of Aging, 72, 187 e5-187 e10. https://doi.org/10.1016/j.neurobiolaging.2018.06.036 |
| [23] | Wang, C., Cai, Y., Gu, Z., et al. (2014) Clinical Profiles of Parkinson’s Disease Associated with Common Leucine-Rich Repeat Kinase 2 and Glucocerebrosidase Genetic Vari-ants in Chinese Individuals. Neurobiology of Aging, 35, 725e1-6.
https://doi.org/10.1016/j.neurobiolaging.2013.08.012 |
| [24] | Gao, C., Pang, H., Luo, X.G., et al. (2013) LRRK2 G2385R Variant Carriers of Female Parkinson’s Disease Are More Susceptible to Motor Fluctuation. Journal of Neu-rology, 260, 2884-2889. https://doi.org/10.1007/s00415-013-7086-9 |
| [25] | Fu, R., Cui, S.S., Du, J.J., et al. (2017) Fatigue Correlates with LRRK2 G2385R Variant in Chinese Parkinson’s Disease Patients. Parkinsonism & Related Disorders, 44, 101-105. https://doi.org/10.1016/j.parkreldis.2017.09.016 |
| [26] | Li, D.W., Gu, Z., Wang, C., et al. (2015) Non-Motor Symptoms in Chinese Parkinson’s Disease Patients with and without LRRK2 G2385R and R1628P Variants. Journal of Neural Transmission (Vienna), 122, 661-667.
https://doi.org/10.1007/s00702-014-1281-4 |
| [27] | Funayama, M., Ohe, K., Amo, T., et al. (2015) CHCHD2 Muta-tions in Autosomal Dominant Late-Onset Parkinson’s Disease: A Genome-Wide Linkage and Sequencing Study. The Lancet Neurology, 14, 274-282.
https://doi.org/10.1016/S1474-4422(14)70266-2 |
| [28] | Li, N.N., Wang, L., Tan, E.K., et al. (2016) Genetic Analysis of CHCHD2 Gene in Chinese Parkinson’s Disease. American Journal of Medical Genetics Part B Neuropsychiatric Genetics, 171, 1148-1152.
https://doi.org/10.1002/ajmg.b.32498 |
| [29] | Lu, Q., Deng, X., Song, Z., et al. (2016) Mutation Analysis of the CHCHD2 Gene in Chinese Han Patients with Parkinson’s Disease. Parkinsonism & Related Disorders, 29, 143-144. https://doi.org/10.1016/j.parkreldis.2016.04.012 |
| [30] | Liu, Z., Guo, J., Li, K., et al. (2015) Mutation Analysis of CHCHD2 Gene in Chinese Familial Parkinson’s Disease. Neurobiology of Aging, 36, 3117e7-3117e8. https://doi.org/10.1016/j.neurobiolaging.2015.08.010 |
| [31] | Yang, N., Zhao, Y., Liu, Z., et al. (2019) Systematically Analyzing Rare Variants of Autosomal-Dominant Genes for Sporadic Parkinson’s Disease in a Chinese Cohort. Neurobiology of Aging, 76, 215e1-215e7.
https://doi.org/10.1016/j.neurobiolaging.2018.11.012 |
| [32] | Shi, C.H., Mao, C.Y., Zhang, S.Y., et al. (2016) CHCHD2 Gene Mutations in Familial and Sporadic Parkinson’s Disease. Neurobiology of Aging, 38, 217e9-217e13. https://doi.org/10.1016/j.neurobiolaging.2015.10.040 |
| [33] | Li, K., Tang, B.S., Guo, J.F., et al. (2013) Analysis of EIF4G1 in Ethnic Chinese. BMC Neurology, 13, 38.
https://doi.org/10.1186/1471-2377-13-38 |
| [34] | Guo, J.F., Sun, Q.Y., Lv, Z.Y., et al. (2012) VPS35 Gene Variants Are Not Associated with Parkinson’s Disease in the Mainland Chinese Population. Parkinsonism & Related Disorders, 18, 983-985.
https://doi.org/10.1016/j.parkreldis.2012.05.002 |
| [35] | Cao, L., Zhang, T., Zheng, L., et al. (2010) The GIGYF2 Variants Are Not Associated with Parkinson’s Disease in the Mainland Chinese Population. Parkinsonism & Related Disorders, 16, 294-297.
https://doi.org/10.1016/j.parkreldis.2009.11.009 |
| [36] | Van der Merwe, C., Jalali Sefid Dashti, Z., Christoffels, A., et al. (2015) Evidence for a Common Biological Pathway Linking Three Parkinson’s Disease-Causing Genes: Parkin, PINK1 and DJ-1. European Journal of Neuroscience, 41, 1113-1125. https://doi.org/10.1111/ejn.12872 |
| [37] | Kalinderi, K., Bostantjopoulou, S. and Fidani, L. (2016) The Genetic Back-ground of Parkinson’s Disease: Current Progress and Future Prospects. Acta Neurologica Scandinavica, 134, 314-326. https://doi.org/10.1111/ane.12563 |
| [38] | Guo, J.F., Dong, X.L., Xu, Q., et al. (2015) Exon Dosage Analysis of Parkin Gene in Chinese Sporadic Parkinson’s Disease. Neuroscience Letters, 604, 47-51. https://doi.org/10.1016/j.neulet.2015.07.046 |
| [39] | Huang, T., Gao, C.Y., Wu, L., et al. (2019) Han Chinese Family with Early-Onset Parkinson’s Disease Carries Novel Compound Heterozygous Mutations in the PARK2 Gene. Brain and Behavior, 9, e01372.
https://doi.org/10.1002/brb3.1372 |
| [40] | Li, H., Yusufujiang, A., Naser, S., et al. (2014) Mutation Analysis of PARK2 in a Uyghur Family with Early-Onset Parkinson’s Disease in Xinjiang, China. Journal of the Neurological Sciences, 342, 21-24.
https://doi.org/10.1016/j.jns.2014.03.044 |
| [41] | Chen, M., Cen, Z., Chen, Y., et al. (2018) Genetic Study of a Par-kinson’s Disease Pedigree Caused by Compound Heterozygous Mutations in PARK2 Gene. Chinese Journal of Medical Genetics, 35, 815-818. |
| [42] | Taylor, J.M., Wu, R.M., Lin, C.H., et al. (2009) Lack of Evidence for Association of a Parkin Promoter Polymorphism with Early-Onset Parkinson’s Disease in a Chinese Population. Parkinsonism & Related Disorders, 15, 149-152.
https://doi.org/10.1016/j.parkreldis.2008.02.010 |
| [43] | Chan, D.K., Mok, V., Ng, P.W., et al. (2008) PARK2 Mu-tations and Clinical Features in a Chinese Population with Early-Onset Parkinson’s Disease. Journal of Neural Trans-mission (Vienna), 115, 715-719.
https://doi.org/10.1007/s00702-007-0011-6 |
| [44] | Wang, Y., Wu, J.J., Liu, F.T., et al. (2017) Olfaction in Parkin Carriers in Chinese Patients with Parkinson Disease. Brain and Behavior, 7, e00680. https://doi.org/10.1002/brb3.680 |
| [45] | Hernandez, D.G., Reed, X. and Singleton, A.B. (2016) Genetics in Parkinson Disease: Mendelian versus Non-Mendelian Inheritance. Journal of Neurochemistry, 139, 59-74. https://doi.org/10.1111/jnc.13593 |
| [46] | Arena, G. and Valente, E.M. (2017) PINK1 in the Limelight: Multiple Functions of an Eclectic Protein in Human Health and Disease. The Journal of Pathology, 241, 251-263. https://doi.org/10.1002/path.4815 |
| [47] | Bonifati, V., Rohe, C.F., Breedveld, G.J., et al. (2005) Early-Onset Par-kinsonism Associated with PINK1 Mutations: Frequency, Genotypes, and Phenotypes. Neurology, 65, 87-95. https://doi.org/10.1212/01.wnl.0000167546.39375.82 |
| [48] | Trinh, J. and Farrer, M. (2013) Advances in the Ge-netics of Parkinson Disease. Nature Reviews Neurology, 9, 445-454.
https://doi.org/10.1038/nrneurol.2013.132 |
| [49] | Li, N., et al. (2020) Whole-Exome Sequencing in Early-Onset Parkinson’s Disease among Ethnic Chinese. Neurobiology of Aging. |
| [50] | Zhang, B.R., Hu, Z.X., Yin, X.Z., et al. (2010) Mutation Analysis of Parkin and PINK1 Genes in Early-Onset Parkinson’s Disease in China. Neuroscience Letters, 477, 19-22. https://doi.org/10.1016/j.neulet.2010.04.026 |
| [51] | Wang, F., Chen, B., Feng, X.L., et al. (2007) PINK1 IVS5-5 G > A Polymorphism May Contribute to the Risk of Late Onset Parkinson Disease in Chinese. Chinese Journal of Medical Genetics, 24, 305-309. |
| [52] | Wang, F., Feng, X., Ma, J., et al. (2006) A Common A340T Variant in PINK1 Gene Associated with Late-Onset Parkinson’s Disease in Chinese. Neuroscience Letters, 410, 121-125. https://doi.org/10.1016/j.neulet.2006.09.080 |
| [53] | 张玉虎. 常染色体隐性遗传早发性帕金森综合征6型PINK1基因的突变分析[J]. 中华医学杂志, 2005, 22(85): 1538-1541. |
| [54] | van der Vlag, M., et al. (2020) The Contribution of Parkin, PINK1 and DJ-1 Genes to Selective Neuronal Degeneration in Parkinson’s Disease. The European Journal of Neuroscience. |
| [55] | Bonifati, V., Rizzu, P., Squitieri, F., et al. (2003) DJ-1(PARK7), a Novel Gene for Autosomal Recessive, Early Onset Parkinsonism. Neurological Sciences, 24, 159-160. https://doi.org/10.1007/s10072-003-0108-0 |
| [56] | Huo, Z., Luo, X., Zhan, X., et al. (2017) Genetic Analysis of Indel Markers in Three Loci Associated with Parkinson’s Disease. PLoS ONE, 12, e0184269. https://doi.org/10.1371/journal.pone.0184269 |
| [57] | Chen, W., Peng, R., Li, T., et al. (2008) Association of the DJ-1 Gene Polymorphism with Sporadic Parkinson’s Disease in Sichuan Province of China. Chinese Journal of Medical Ge-netics, 25, 566-569. |
| [58] | Pan, L.S., Wang, Z., Ding, D., et al. (2016) Lack of Association between the ATP13A2 A746T Variant and Parkinson’s Disease Susceptibility in Han Chinese: A Meta-Analysis. International Journal of Neuroscience, 126, 593-599.
https://doi.org/10.3109/00207454.2015.1035377 |
| [59] | Li, G., Zhang, Z., Xia, H., et al. (2014) Analysis of Thr12Met and Ala1144Thr Mutations of the ATP13A2 Gene in Parkinson’s Disease Patients in Xinjiang Uygur and Han Ethnic Groups. Medical Science Monitor, 20, 2177-2182.
https://doi.org/10.12659/MSM.892821 |
| [60] | Shi, C., Li, F., Yang, J., et al. (2016) DNAJC6 Mutations Are Not Common Causes of Early Onset Parkinson’s Disease in Chinese Han Population. Neuroscience Letters, 634, 60-62. https://doi.org/10.1016/j.neulet.2016.09.044 |
| [61] | Wang, L., Cheng, L., Li, N.N., et al. (2016) Association of Four New Candidate Genetic Variants with Parkinson’s Disease in a Han Chinese Population. American Journal of Medical Genetics Part B Neuropsychiatric Genetics, 171, 342-347. https://doi.org/10.1002/ajmg.b.32410 |
| [62] | Mullin, S., Hughes, D., Mehta, A., et al. (2019) Neurological Effects of Glucocerebrosidase Gene Mutations. European Journal of Neurology, 26, 388-e29. https://doi.org/10.1111/ene.13837 |
| [63] | Sidransky, E., Nalls, M.A., Aasly, J.O., et al. (2009) Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson’s Disease. The New England Journal of Medicine, 361, 1651-1661. https://doi.org/10.1056/NEJMoa0901281 |
| [64] | Migdalska-Richards, A. and Schapira, A.H. (2016) The Relationship between Glucocerebrosidase Mutations and Parkinson Disease. Journal of Neurochem-istry, 139, 77-90. https://doi.org/10.1111/jnc.13385 |
| [65] | Zhang, Y., et al. (2018) GBAIntegrated Genetic Analysis of Racial Differences of Common Variants in Parkinson’s Disease: A Meta-Analysis. Frontiers in Molecular Neu-roscience, 11, 43. https://doi.org/10.3389/fnmol.2018.00043 |
| [66] | Guo, J.F., Li, K., Yu, R.L., et al. (2015) Poly-genic Determinants of Parkinson’s Disease in a Chinese Population. Neurobiology of Aging, 36, 1765e1-1765e6. https://doi.org/10.1016/j.neurobiolaging.2014.12.030 |
| [67] | Shi, C., Zheng, Z., Wang, Q., et al. (2016) Exploring the Effects of Genetic Variants on Clinical Profiles of Parkinson’s Disease Assessed by the Unified Parkinson’s Disease Rating Scale and the Hoehn-Yahr Stage. PLoS ONE, 11, e0155758. https://doi.org/10.1371/journal.pone.0155758 |
| [68] | Yu, Z., Wang, T., Xu, J., et al. (2015) Mutations in the Glucocerebrosidase Gene Are Responsible for Chinese Patients with Parkinson’s Disease. Journal of Human Genetics, 60, 85-90. https://doi.org/10.1038/jhg.2014.110 |
| [69] | Fan, K., Tang, B.S., Wang, Y.Q., et al. (2016) The GBA, DYRK1A and MS4A6A Polymorphisms Influence the Age at Onset of Chinese Parkinson Patients. Neuroscience Let-ters, 621, 133-136.
https://doi.org/10.1016/j.neulet.2016.04.014 |
| [70] | Wu, Y.R., Chen, C.M., Chao, C.Y., et al. (2007) Glucocerebrosidase Gene Mutation Is a Risk Factor for Early Onset of Parkinson Disease among Taiwanese. Journal of Neurology, Neurosurgery, and Psychiatry, 78, 977-979.
https://doi.org/10.1136/jnnp.2006.105940 |
| [71] | Hu, F.Y., Xi, J., Guo, J., et al. (2010) Association of the Glucocerebrosidase N370S Allele with Parkinson’s Disease in Two Separate Chinese Han Populations of Mainland China. European Journal of Neurology, 17, 1476-1478.
https://doi.org/10.1111/j.1468-1331.2010.03097.x |
| [72] | Sidransky, E., et al. (2009) Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson’s Disease. The New England Journal of Medicine, 361, 1651-1661. https://doi.org/10.1056/NEJMoa0901281 |
| [73] | Dan, X., Wang, C., Zhang, J., et al. (2016) Association between Common Genetic Risk Variants and Depression in Parkinson’s Disease: A dPD Study in Chinese. Parkinsonism & Re-lated Disorders, 33, 122-126.
https://doi.org/10.1016/j.parkreldis.2016.09.029 |
| [74] | Pascale, E., Di Battista, M.E., Rubino, A., et al. (2016) Ge-netic Architecture of MAPT Gene Region in Parkinson Disease Subtypes. Frontiers in Cellular Neuroscience, 10, 96. https://doi.org/10.3389/fncel.2016.00096 |
| [75] | Fagan, E.S. and Pihlstrom, L. (2017) Genetic Risk Factors for Cog-nitive Decline in Parkinson’s Disease: A Review of the Literature. European Journal of Neurology, 24, 561-e20. https://doi.org/10.1111/ene.13258 |
| [76] | Kalinderi, K., Fidani, L. and Bostantjopoulou, S. (2009) From 1997 to 2007: A Decade Journey through the H1 Haplotype on 17q21 Chromosome. Parkinsonism & Related Disorders, 15, 2-5.
https://doi.org/10.1016/j.parkreldis.2008.03.001 |
| [77] | Yu, L., Huang, J., Zhai, D., et al. (2014) MAPT rs242562 and GSK3B rs334558 Are Associated with Parkinson’s Disease in Central China. BMC Neuroscience, 15, 54. https://doi.org/10.1186/1471-2202-15-54 |
| [78] | Dan, X., Wang, C., Ma, J., et al. (2014) MAPT IVS1 + 124 C > G Modifies Risk of LRRK2 G2385R for Parkinson’s Disease in Chinese Individuals. Neurobiology of Aging, 35, 1780e7-1780e10.
https://doi.org/10.1016/j.neurobiolaging.2014.01.025 |
| [79] | Wang, G., Huang, Y., Chen, W., et al. (2016) Variants in the SNCA Gene Associate with Motor Progression While Variants in the MAPT Gene Associate with the Severity of Parkinson’s Disease. Parkinsonism & Related Disorders, 24, 89-94. https://doi.org/10.1016/j.parkreldis.2015.12.018 |
