Genetics of progressive supranuclear palsy in a Chinese population
Background: Genetics plays an important role in progressive supranuclear palsy (PSP) and remains poorly understood. A detailed literature search identified 19 PSP-associated genes: MAPT, LRRK2, LRP10, DCTN1, GRN, NPC1, PARK, TARDBP, TBK1, BSN, GBA, STX6, EIF2AK3, MOBP, DUSP10, SLCO1A2, RUNX2, CXCR4,...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999612200211X |
| _version_ | 1817998317513080832 |
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| author | Xuewen Xiao Qijie Yang Yafei Wen Bin Jiao Xinxin Liao Yafang Zhou Ling Weng Hui Liu Tianyan Xu Yuan Zhu Lina Guo Lu Zhou Xin Wang Xixi Liu Xiangyun Bi Yingzi Liu Sizhe Zhang Weiwei Zhang Jinchen Li Beisha Tang Lu Shen |
| author_facet | Xuewen Xiao Qijie Yang Yafei Wen Bin Jiao Xinxin Liao Yafang Zhou Ling Weng Hui Liu Tianyan Xu Yuan Zhu Lina Guo Lu Zhou Xin Wang Xixi Liu Xiangyun Bi Yingzi Liu Sizhe Zhang Weiwei Zhang Jinchen Li Beisha Tang Lu Shen |
| author_sort | Xuewen Xiao |
| collection | DOAJ |
| description | Background: Genetics plays an important role in progressive supranuclear palsy (PSP) and remains poorly understood. A detailed literature search identified 19 PSP-associated genes: MAPT, LRRK2, LRP10, DCTN1, GRN, NPC1, PARK, TARDBP, TBK1, BSN, GBA, STX6, EIF2AK3, MOBP, DUSP10, SLCO1A2, RUNX2, CXCR4, and APOE. To date, genetic studies on PSP have focused on Caucasian population. The gaps in PSP genetic study on East Asian populations need to be filled. Methods: Exon and flanking regions of the PSP-associated genes were sequenced in 104 patients with PSP and 488 healthy controls. Common variant-based association analysis and gene-based association tests of rare variants were performed using PLINK 1.9 and the sequence kernel association test-optimal, respectively. Additionally, the association of APOE and MAPT genotypes with PSP was evaluated. The above association analyses were repeated among probable PSP patients. Finally, PLINK 1.9 was used to test variants associated with the onset age of PSP. Results: A rare non-pathogenic variant of MAPT (c.425C > T,p.A142V) was detected in a PSP patient. No common variants were significantly associated with PSP. In both the rare-variant and the rare-damaging-variant groups, the combined effect for GBA reached statistical significance (p = 1.43 × 10−3, p = 4.98 × 10−4). The result between APOE, MAPT genotypes and PSP risk were inconsistent across all PSP group and probably PSP group. Conclusions: The pathogenic variant in MAPT were uncommon in PSP patients. Moreover, GBA gene was likely to increase the risk of PSP, and GBA-associated diseases were beyond α-synucleinopathies. The association between APOE, MAPT and PSP is still unclear among the non-Caucasian population. |
| first_indexed | 2024-04-14T02:51:21Z |
| format | Article |
| id | doaj.art-667382c252d245808198af7c31e6581e |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-04-14T02:51:21Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-667382c252d245808198af7c31e6581e2022-12-22T02:16:16ZengElsevierNeurobiology of Disease1095-953X2022-10-01172105819Genetics of progressive supranuclear palsy in a Chinese populationXuewen Xiao0Qijie Yang1Yafei Wen2Bin Jiao3Xinxin Liao4Yafang Zhou5Ling Weng6Hui Liu7Tianyan Xu8Yuan Zhu9Lina Guo10Lu Zhou11Xin Wang12Xixi Liu13Xiangyun Bi14Yingzi Liu15Sizhe Zhang16Weiwei Zhang17Jinchen Li18Beisha Tang19Lu Shen20Department of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Central South University, Changsha, China; Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, China; Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, ChinaDepartment of Geriatric, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Geriatric, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Radiology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Central South University, Changsha, ChinaDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Central South University, Changsha, China; Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, China; Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China; Corresponding author at: Xiangya Hospital, Central South University, Changsha, China.Background: Genetics plays an important role in progressive supranuclear palsy (PSP) and remains poorly understood. A detailed literature search identified 19 PSP-associated genes: MAPT, LRRK2, LRP10, DCTN1, GRN, NPC1, PARK, TARDBP, TBK1, BSN, GBA, STX6, EIF2AK3, MOBP, DUSP10, SLCO1A2, RUNX2, CXCR4, and APOE. To date, genetic studies on PSP have focused on Caucasian population. The gaps in PSP genetic study on East Asian populations need to be filled. Methods: Exon and flanking regions of the PSP-associated genes were sequenced in 104 patients with PSP and 488 healthy controls. Common variant-based association analysis and gene-based association tests of rare variants were performed using PLINK 1.9 and the sequence kernel association test-optimal, respectively. Additionally, the association of APOE and MAPT genotypes with PSP was evaluated. The above association analyses were repeated among probable PSP patients. Finally, PLINK 1.9 was used to test variants associated with the onset age of PSP. Results: A rare non-pathogenic variant of MAPT (c.425C > T,p.A142V) was detected in a PSP patient. No common variants were significantly associated with PSP. In both the rare-variant and the rare-damaging-variant groups, the combined effect for GBA reached statistical significance (p = 1.43 × 10−3, p = 4.98 × 10−4). The result between APOE, MAPT genotypes and PSP risk were inconsistent across all PSP group and probably PSP group. Conclusions: The pathogenic variant in MAPT were uncommon in PSP patients. Moreover, GBA gene was likely to increase the risk of PSP, and GBA-associated diseases were beyond α-synucleinopathies. The association between APOE, MAPT and PSP is still unclear among the non-Caucasian population.http://www.sciencedirect.com/science/article/pii/S096999612200211XProgressive supranuclear palsyGeneticsGBAMAPTAPOE |
| spellingShingle | Xuewen Xiao Qijie Yang Yafei Wen Bin Jiao Xinxin Liao Yafang Zhou Ling Weng Hui Liu Tianyan Xu Yuan Zhu Lina Guo Lu Zhou Xin Wang Xixi Liu Xiangyun Bi Yingzi Liu Sizhe Zhang Weiwei Zhang Jinchen Li Beisha Tang Lu Shen Genetics of progressive supranuclear palsy in a Chinese population Neurobiology of Disease Progressive supranuclear palsy Genetics GBA MAPT APOE |
| title | Genetics of progressive supranuclear palsy in a Chinese population |
| title_full | Genetics of progressive supranuclear palsy in a Chinese population |
| title_fullStr | Genetics of progressive supranuclear palsy in a Chinese population |
| title_full_unstemmed | Genetics of progressive supranuclear palsy in a Chinese population |
| title_short | Genetics of progressive supranuclear palsy in a Chinese population |
| title_sort | genetics of progressive supranuclear palsy in a chinese population |
| topic | Progressive supranuclear palsy Genetics GBA MAPT APOE |
| url | http://www.sciencedirect.com/science/article/pii/S096999612200211X |
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