ATXN2 trinucleotide repeat length correlates with risk of ALS

NEUROBIOLOGY OF AGING

卷:51

Article

Sproviero, William¹  Shatunov, Aleksey¹  Stahl, Daniel²  Shoai, Maryam³  van Rheenen, Wouter⁴  Jones, Ashley R.¹  Al-Sarraj, Safa⁵  Andersen, Peter M.⁶  Bonini, Nancy M.⁷  Conforti, Francesca L.⁸  Van Damme, Philip^9,10,11  Daoud, Hussein¹²  Amador, Maria Del Mar¹³  Forzan, Monica¹⁴  Gaastra, Ben¹  Gellera, Cinzia¹⁵  Gitler, Aaron D.¹⁶  Hardy, John³  Fratta, Pietro¹⁷  La Bella, Vincenzo¹⁸  Le Ber, Isabelle^1,19,20  Van Langenhove, Tim^21,22,23  Lattante, Serena¹⁹  Lee, Yi-Chung^24,25,26  Malaspina, Andrea^27,28  Meininger, Vincent^29,30  Orrell, Richard³¹  Rademakers, Rosa³²  Robberecht, Wim^10,11  Rouleau, Guy¹²  Ross, Owen A.³²  Salachas, Francois^13,19  Sidle, Katie³  Smith, Bradley N.¹  Soong, Bing-Wen^24,25,26  Soraru, Gianni³³  Stevanin, Giovanni^19,34  Kabashi, Edor¹⁹  Troakes, Claire¹  van Broeckhoven, Christine^21,22  Veldink, Jan H.⁴  van den Berg, Leonard H.⁴  Shaw, Christopher E.¹  Powell, John F.¹  Al-Chalabi, Ammar¹ 

[1] Kings Coll London, Maurice Wohl Clin Neurosci Inst, Dept Basic & Clin Neurosci, 5 Cutcombe Rd,Camberwell, London SE5 9RX, England

[2] Kings Coll London, Inst Psychiat, Dept Biostatist, Psychol & Neurosci, London, England

[3] UCL, Inst Neurol, Dept Mol Neurosci, London, England

[4] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Inst Neurosci, Dept Neurol, Utrecht, Netherlands

[5] NHS Fdn Trust, Kings Coll Hosp, Dept Clin Neuropathol, London, England

[6] Umed Univ, Dept Pharmacol & Clin Neurosci, Umed, Sweden

[7] Univ Pennsylvania, Dept Biol, Philadelphia, PA USA

[8] CNR, Inst Neurol Sci, Cosenza, Italy

[9] Univ Hosp Leuven, Dept Neurol, Leuven, Belgium

[10] VIB, Vesalius Res Ctr, Leuven, Belgium

[11] Univ Leuven, KU Leuven, Dis LIND, Leuven, Belgium

[12] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada

[13] Grp Hosp Pitie Salpetriere, APHP, ALS Paris ALS Ctr Rare, Dept Nervous Syst Dis, Paris, France

[14] Univ Padua, Dept Woman & Child Hlth, Clin Genet Unit, Padua, Italy

[15] Fdn IRCCS Ist Neurol Carlo Besta, Milan, Italy

[16] Stanford Univ, Sch Med, Dept Genet, Stanford, CA USA

[17] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London, England

[18] Univ Palermo, ALS Clin Res Ctr, Bio Ne C, Palermo, Italy

[19] UPMC Univ Paris 06, Sorbonne Univ, CNRS UMR 7225, Inserm U1127,Inst Cerveau & Moelle Epiniere ICM,U, Paris, France

[20] Hop Univ Pitie Salpetriere Charles Foix, AP HP, Ctr Reference Demences Rares, Dept Neurol, Paris, France

[21] VIB, Neurodegenerat Brain Dis Grp, Dept Mol Genet, Antwerp, Belgium

[22] Univ Antwerp, Insititute Born Bunge, Neurogenet Lab, Antwerp, Belgium

[23] Univ Antwerp Hosp, Dept Neurol, Edegem, Belgium

[24] Taipei Vet Gen Hosp, Dept Neurol, Taipei, Taiwan

[25] Natl Yang Ming Univ, Sch Med, Dept Neurol, Taipei, Taiwan

[26] Natl Yang Ming Univ, Brain Res Ctr, Taipei, Taiwan

[27] Essex MND Care Ctr, North East London, London, England

[28] Barts London Sch Med Dent, Inst Cell & Mol Med, Neurosci & Trauma Ctr, Barts Hlth NHS Trust, London, England

[29] Hop La Pitie Salpetriere, Inst Rech Translationnelle Neurosci A ICM, Paris, France

[30] Hopi Pitie Salpetriere, Reseau SLA IdF, Paris, France

[31] UCL, Inst Neurol, Dept Clin Neurosci, London, England

[32] Mayo Clin, Dept Neurosci, Jacksonville, FL USA

[33] Univ Padua, Dept Neurosci, Padua, Italy

[34] Ecole Prat Hautes Etud, Neurogenet Team, Paris, France

关键词: ATXN2;    SCA2;    ALS;    CAG;    Expansion;    Intermediate expansion;    Trinucleotide repeat;    Amyotrophic lateral sclerosis;    Age of onset;    Risk;    Exponential risk;    Triplet;   

DOI  :  10.1016/j.neurobiolaging.2016.11.010

来源: Elsevier

【 摘 要 】

We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37e3.94]; p = 6 x 10(-18)), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R-2 = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk. (C) 2016 The Author(s). Published by Elsevier Inc.

【 授权许可】

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