UNC13A influences survival in Italian amyotrophic lateral sclerosis patients: a population-based study.
UNC13A influences survival in Italian amyotrophic lateral sclerosis patients: a population-based study.
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DOI：
10.1016/j.neurobiolaging.2012.07.016
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发表时间：
2013-01
影响因子：
4.2
通讯作者：
Calvo A
中科院分区：
文献类型：
--
作者：
Chiò A;Mora G;Restagno G;Brunetti M;Ossola I;Barberis M;Ferrucci L;Canosa A;Manera U;Moglia C;Fuda G;Traynor BJ;Calvo A
位于19p13.3染色体上UNC13A基因内含子内的常见变异rs12608932已被认为影响北欧血统患者对ALS的易感性和生存率。为了进一步检验这种可能性，我们在500名意大利ALS患者和1457名意大利对照样本的人群队列中评估了rs12608932与易感性和生存率的关系。虽然在我们的研究中rs12608932与ALS易感性无关（p=0.124），但在隐性模型下，它与生存显著相关（AA/AC基因型的中位生存= 3.5年[IQR 2.2-6.4]; CC = 2.5年[IQR 1.6-4.2]; p=0.017）。此外，在Cox多变量分析中，rs12608932基因型仍然是一个独立的预后因素，校正了其他已知影响生存的因素（p=0.023）。总的来说，rs12608932的次要等位基因携带状态与ALS患者1年的生存减少密切相关，使其成为表型变异的重要决定因素。UNC13A作为散发性ALS患者预后调节剂的鉴定可能为减缓疾病进展提供新的治疗靶点。
The common variant rs12608932, located within an intron of UNC13A gene on chromosome 19p13.3, has been suggested to influence susceptibility to ALS, as well as survival, in patients of north European descent. To examine this possibility further, we evaluated the association of rs12608932 with susceptibility and survival in a population-based cohort of 500 Italian ALS patients and 1,457 Italian control samples. Although rs12608932 was not associated to ALS susceptibility in our series (p=0.124), it was significantly associated with survival under the recessive model (median survival for AA/AC genotypes = 3.5 years [IQR 2.2–6.4]; CC = 2.5 years [IQR 1.6–4.2]; p=0.017). Furthermore, rs12608932 genotype remained an independent prognostic factor in Cox multivariable analysis adjusting for other factors known to influence survival (p=0.023). Overall, minor allele carrier status of rs12608932 was strongly associated with an ~1-year reduction of survival in ALS patients, making it a significant determinant of phenotype variation. The identification of UNC13A as a modifier of prognosis among sporadic ALS patients potentially provides a new therapeutic target aimed at slowing disease progression.
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影响因子：
4.5
作者：
Melzer D;Perry JR;Hernandez D;Corsi AM;Stevens K;Rafferty I;Lauretani F;Murray A;Gibbs JR;Paolisso G;Rafiq S;Simon-Sanchez J;Lango H;Scholz S;Weedon MN;Arepalli S;Rice N;Washecka N;Hurst A;Britton A;Henley W;van de Leemput J;Li R;Newman AB;Tranah G;Harris T;Panicker V;Dayan C;Bennett A;McCarthy MI;Ruokonen A;Jarvelin MR;Guralnik J;Bandinelli S;Frayling TM;Singleton A;Ferrucci L
通讯作者：
Ferrucci L
影响因子：
48
作者：
Laaksovirta, Hannu;Peuralinna, Terhi;Schymick, Jennifer C.;Scholz, Sonja W.;Lai, Shaoi-Lin;Myllykangas, Liisa;Sulkava, Raimo;Jansson, Lilja;Hernandez, Dena G.;Gibbs, J. Raphael;Nalls, Michael A.;Heckerman, David;Tienari, Pentti J.;Traynor, Bryan J.
通讯作者：
Traynor, Bryan J.
影响因子：
4.2
作者：
Sabatelli M;Conforti FL;Zollino M;Mora G;Monsurrò MR;Volanti P;Marinou K;Salvi F;Corbo M;Giannini F;Battistini S;Penco S;Lunetta C;Quattrone A;Gambardella A;Logroscino G;Simone I;Bartolomei I;Pisano F;Tedeschi G;Conte A;Spataro R;La Bella V;Caponnetto C;Mancardi G;Mandich P;Sola P;Mandrioli J;Renton AE;Majounie E;Abramzon Y;Marrosu F;Marrosu MG;Murru MR;Sotgiu MA;Pugliatti M;Rodolico C;ITALSGEN Consortium;Moglia C;Calvo A;Ossola I;Brunetti M;Traynor BJ;Borghero G;Restagno G;Chiò A
通讯作者：
Chiò A
影响因子：
11
作者：
O'Toole, O.;Traynor, B. J.;Hardiman, O.
通讯作者：
Hardiman, O.
DOI：
10.1111/j.1532-5415.2000.tb03873.x
发表时间：
2000-12-01
影响因子：
6.3
作者：
Ferrucci, L;Bandinelli, S;Guralnik, JM
通讯作者：
Guralnik, JM