MAPT haplotype diversity in multiple system atrophy.
MAPT haplotype diversity in multiple system atrophy.
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DOI：
10.1016/j.parkreldis.2016.06.010
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发表时间：
2016-09
影响因子：
4.1
通讯作者：
Ross OA
中科院分区：
文献类型：
--
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
多系统萎缩症（MSA）是一种罕见的进行性神经退行性疾病。 MSA 最初被认为是散发性的，但与 SNCA、COQ2 和 LRRK2 等基因相关的报告表明，该疾病与遗传有关。 MAPT 与多种神经退行性疾病有关，我们之前在 61 个病理确诊病例中报道了 MAPT H2 单倍型与 MSA 的保护性关联。在本研究中，我们使用六个 MAPT 标记 SNP 评估了 MSA 患者的完整 MAPT 单倍型多样性。我们对总共 127 例病理确诊的 MSA 病例、86 例临床诊断的 MSA 患者和 1312 例对照进行了基因分型。我们在病理确诊病例中发现了四个显着的关联信号，其中两个来自保护性单倍型 H2（MSA：16.2％，对照：22.7％，p = 0.024）和 H1E（MSA：3.0％，对照：9.0％，p = 0.014），两个来自罕见风险单倍型 H1x（MSA：3.7％，对照：1.3％， p=0.030）和 H1J（MSA：3.0%，对照：0.9%，p=0.021）。我们评估了 MSA 亚型与常见保护性 H2 单倍型的关联，发现具有一定程度 MSA-C（MSA-C 或 MSA 混合）的 MSA 患者与对照组存在显着差异，在我们的病理证实系列中，仅 8.6% 的患者出现 H2（P<0.0001）。我们的研究结果进一步证明 MAPT 变异与 MSA 风险相关。有趣的是，我们的结果表明，与 H2 的 MSA-P 相比，MSA-C 的效应大小更大。需要在更大规模的病理学证实的 MSA 系列中进行额外的遗传学研究和荟萃分析研究，以充分评估 MAPT 和其他基因在 MSA 中的作用。
Multiple system atrophy (MSA) is a rare progressive neurodegenerative disorder. MSA was originally considered exclusively sporadic but reports of association with genes such as SNCA, COQ2 and LRRK2 have demonstrated that there is a genetic contribution to the disease. MAPT has been associated with several neurodegenerative diseases and we previously reported a protective association of the MAPT H2 haplotype with MSA in 61 pathologically confirmed cases. In the present study, we assessed the full MAPT haplotype diversity in MSA patients using six MAPT tagging SNPs. We genotyped a total of 127 pathologically confirmed MSA cases, 86 patients with clinically diagnosed MSA and 1312 controls. We identified four significant association signals in our pathologically confirmed cases, two from the protective haplotypes H2 (MSA:16.2%, Controls:22.7%, p=0.024) and H1E (MSA:3.0%, Controls:9.0%, p=0.014), and two from the rare risk haplotypes H1x (MSA:3.7%, Controls:1.3%, p=0.030) and H1J (MSA:3.0%, Controls:0.9%, p=0.021). We evaluated the association of MSA subtypes with the common protective H2 haplotype and found a significant difference with controls for MSA patients with some degree of MSA-C (MSA-C or MSA-mixed), for whom H2 occurred in only 8.6% of patients in our pathologically confirmed series (P<0.0001). Our findings provide further evidence that MAPT variation is associated with risk of MSA. Interestingly, our results suggest a greater effect size in the MSA-C compared to MSA-P for H2. Additional genetic studies in larger pathologically confirmed MSA series and meta-analytic studies will be needed to fully assess the role of MAPT and other genes in MSA.
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影响因子：
11.2
作者：
Scholz, Sonja W.;Houlden, Henry;Schulte, Claudia;Sharma, Manu;Li, Abi;Berg, Daniela;Melchers, Anna;Paudel, Reema;Gibbs, J. Raphael;Simon-Sanchez, Javier;Paisan-Ruiz, Coro;Bras, Jose;Ding, Jinhui;Chen, Honglei;Traynor, Bryan J.;Arepalli, Sampath;Zonozi, Ryan R.;Revesz, Tamas;Holton, Janice;Wood, Nick;Lees, Andrew;Oertel, Wolfgang;Wuellner, Ullrich;Goldwurm, Stefano;Pellecchia, Maria Teresa;Illig, Thomas;Riess, Olaf;Fernandez, Hubert H.;Rodriguez, Ramon L.;Okun, Michael S.;Poewe, Werner;Wenning, Gregor K.;Hardy, John A.;Singleton, Andrew B.;Gasser, Thomas
通讯作者：
Gasser, Thomas
影响因子：
5.3
作者：
Mitsui, Jun;Matsukawa, Takashi;Sasaki, Hidenao;Yabe, Ichiro;Matsushima, Masaaki;Duerr, Alexandra;Brice, Alexis;Takashima, Hiroshi;Kikuchi, Akio;Aoki, Masashi;Ishiura, Hiroyuki;Yasuda, Tsutomu;Date, Hidetoshi;Ahsan, Budrul;Iwata, Atsushi;Goto, Jun;Ichikawa, Yaeko;Nakahara, Yasuo;Momose, Yoshio;Takahashi, Yuji;Hara, Kenju;Kakita, Akiyoshi;Yamada, Mitsunori;Takahashi, Hitoshi;Onodera, Osamu;Nishizawa, Masatoyo;Watanabe, Hirohisa;Ito, Mizuki;Sobue, Gen;Ishikawa, Kinya;Mizusawa, Hidehiro;Kanai, Kazuaki;Hattori, Takamichi;Kuwabara, Satoshi;Arai, Kimihito;Koyano, Shigeru;Kuroiwa, Yoshiyuki;Hasegawa, Kazuko;Yuasa, Tatsuhiko;Yasui, Kenichi;Nakashima, Kenji;Ito, Hijiri;Izumi, Yuishin;Kaji, Ryuji;Kato, Takeo;Kusunoki, Susumu;Osaki, Yasushi;Horiuchi, Masahiro;Kondo, Tomoyoshi;Murayama, Shigeo;Hattori, Nobutaka;Yamamoto, Mitsutoshi;Murata, Miho;Satake, Wataru;Toda, Tatsushi;Filla, Alessandro;Klockgether, Thomas;Wuellner, Ullrich;Nicholson, Garth;Gilman, Sid;Tanner, Caroline M.;Kukull, Walter A.;Stern, Mathew B.;Lee, Virginia M. -Y.;Trojanowski, John Q.;Masliah, Eliezer;Low, Phillip A.;Sandroni, Paola;Ozelius, Laurie J.;Foroud, Tatiana;Tsuji, Shoji
通讯作者：
Tsuji, Shoji
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
DOI：
10.1016/s1474-4422(12)70327-7
发表时间：
2013-03
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Wenning GK;Geser F;Krismer F;Seppi K;Duerr S;Boesch S;Köllensperger M;Goebel G;Pfeiffer KP;Barone P;Pellecchia MT;Quinn NP;Koukouni V;Fowler CJ;Schrag A;Mathias CJ;Giladi N;Gurevich T;Dupont E;Ostergaard K;Nilsson CF;Widner H;Oertel W;Eggert KM;Albanese A;del Sorbo F;Tolosa E;Cardozo A;Deuschl G;Hellriegel H;Klockgether T;Dodel R;Sampaio C;Coelho M;Djaldetti R;Melamed E;Gasser T;Kamm C;Meco G;Colosimo C;Rascol O;Meissner WG;Tison F;Poewe W;European Multiple System Atrophy Study Group
通讯作者：
European Multiple System Atrophy Study Group
影响因子：
9.9
作者：
Gilman, S.;Wenning, G. K.;Vidailhet, M.
通讯作者：
Vidailhet, M.