MAPT subhaplotypes in corticobasal degeneration: assessing associations with disease risk, severity of tau pathology, and clinical features.
MAPT subhaplotypes in corticobasal degeneration: assessing associations with disease risk, severity of tau pathology, and clinical features.
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DOI：
10.1186/s40478-020-01097-z
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发表时间：
2020-12-07
影响因子：
7.1
通讯作者：
Heckman MG
中科院分区：
文献类型：
--
作者：
Valentino RR;Koga S;Walton RL;Soto-Beasley AI;Kouri N;DeTure MA;Murray ME;Johnson PW;Petersen RC;Boeve BF;Uitti RJ;Wszolek ZK;Dickson DW;Ross OA;Heckman MG
微管相关的蛋白质tau（MAPT）H1单倍型是皮质型变性的强遗传风险因素（CBD），但是，特定的H1亚脑质型关联尚不很好，并且尚不清楚任何MAPT单倍型是否影响单倍型或CBD中的临床表现。具有CBD风险，TAU病理的严重程度（以盘绕体的半定量分数测量，神经原纤维缠结，星形胶质斑块和神经胶质线，CBD发作的年龄和疾病持续时间（P <）（P <），MAPT型单倍型（以半定量分数为单位）。 0.0026被认为是显着的），我们证实了MAPT H2单倍型与CBD风险改善（优势比= 0.26，P = 2×10-12）和还观察到H1D亚脑型型与CBD风险增加（赔率= 1.76，p = 0.002），尽管在校正多个测试后，H1C单倍型与CBD的风险较高，但比率= 1.49，p = 0.009）。疾病持续时间。在驱动tau病理或临床特征方面发挥了重要作用。存在于CBD与相关的tauopathy进行性腹膜上麻痹之间，H2，H1D和H1C表现出与这两种疾病的关联。
The microtubule-associated protein tau (MAPT) H1 haplotype is the strongest genetic risk factor for corticobasal degeneration (CBD). However, the specific H1 subhaplotype association is not well defined, and it is not clear whether any MAPT haplotypes influence severity of tau pathology or clinical presentation in CBD. Therefore, in the current study we examined 230 neuropathologically confirmed CBD cases and 1312 controls in order to assess associations of MAPT haplotypes with risk of CBD, severity of tau pathology (measured as semi-quantitative scores for coiled bodies, neurofibrillary tangles, astrocytic plaques, and neuropil threads), age of CBD onset, and disease duration. After correcting for multiple testing (P < 0.0026 considered as significant), we confirmed the strong association between the MAPT H2 haplotype and decreased risk of CBD (Odds ratio = 0.26, P = 2 × 10−12), and also observed a novel association between the H1d subhaplotype and an increased CBD risk (Odds ratio = 1.76, P = 0.002). Additionally, although not statistically significant after correcting for multiple testing, the H1c haplotype was associated with a higher risk of CBD (Odds ratio = 1.49, P = 0.009). No MAPT haplotypes were significantly associated with any tau pathology measures, age of CBD onset, or disease duration. Though replication will be important and there is potential that population stratification could have influenced our findings, these results suggest that several MAPT H1 subhaplotypes are primarily responsible for the strong association between MAPT H1 and risk of CBD, but that H1 subhaplotypes are unlikely to play a major role in driving tau pathology or clinical features. Our findings also indicate that similarities in MAPT haplotype risk-factor profile exist between CBD and the related tauopathy progressive supranuclear palsy, with H2, H1d, and H1c displaying associations with both diseases.
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影响因子：
4.1
作者：
Labbé C;Heckman MG;Lorenzo-Betancor O;Murray ME;Ogaki K;Soto-Ortolaza AI;Walton RL;Fujioka S;Koga S;Uitti RJ;van Gerpen JA;Petersen RC;Graff-Radford NR;Younkin SG;Boeve BF;Cheshire WP Jr;Low PA;Sandroni P;Coon EA;Singer W;Wszolek ZK;Dickson DW;Ross OA
通讯作者：
Ross OA
影响因子：
5.6
作者：
Scholz SW;Bras J
通讯作者：
Bras J
影响因子：
4.2
作者：
Vandrovcova, Jana;Pittman, Alan M.;de Silva, Rohan
通讯作者：
de Silva, Rohan
影响因子：
--
作者：
Webb, Amy;Miller, Bruce;Wilhelmsen, Kirk C.
通讯作者：
Wilhelmsen, Kirk C.
影响因子：
4.1
作者：
Labbé C;Soto-Ortolaza AI;Rayaprolu S;Harriott AM;Strongosky AJ;Uitti RJ;Van Gerpen JA;Wszolek ZK;Ross OA
通讯作者：
Ross OA