Defining the association of TMEM106B variants among frontotemporal lobar degeneration patients with GRN mutations and C9orf72 repeat expansions

Serena Lattante, Isabelle Le Ber, Daniela Galimberti, Maria Serpente, Sophie Rivaud-Péchoux, Agnès Camuzat, Fabienne Clot, Chiara Fenoglio, Elio Scarpini, Alexis Brice, Edor Kabashi, Sophie Auriacombe, Alexis Brice, Frédéric Blanc, Mira Didic, Bruno Dubois, Charles Duyckaerts, Marie-Odile Habert, Véronique Golfier, Eric GuedjDidier Hannequin, Lucette Lacomblez, Isabelle Le Ber, Richard Levy, Vincent Meininger, Bernard-François Michel, Florence Pasquier, Catherine Thomas-Anterion, Michèle Puel, François Salachas, François Sellal, Martine Vercelletto, Patrice Verpillat

Risultato della ricerca: Contributo in rivistaArticolo in rivista

21 Citazioni (Scopus)

Abstract

TMEM106B was identified as a risk factor for frontotemporal lobar degeneration (FTD) with TAR DNA-binding protein 43 kDa inclusions. It has been reported that variants in this gene are genetic modifiers of the disease and that this association is stronger in patients carrying a GRN mutation or a pathogenic expansion in chromosome 9 open reading frame 72 (C9orf72) gene. Here, we investigated the contribution of TMEM106B polymorphisms in cohorts of FTD and FTD with amyotrophic lateral sclerosis patients from France and Italy. Patients carrying the C9orf72 expansion (n = 145) and patients with GRN mutations (n = 76) were compared with a group of FTD patients (n = 384) negative for mutations and to a group of healthy controls (n = 552). In our cohorts, the presence of the C9orf72 expansion did not correlate with TMEM106B genotypes but the association was very strong in individuals with pathogenic GRN mutations (p = 9.54 × 10(-6)). Our data suggest that TMEM106B genotypes differ in FTD patient cohorts and strengthen the protective role of TMEM106B in GRN carriers. Further studies are needed to determine whether TMEM106B polymorphisms are associated with other genetic causes for FTD, including C9orf72 repeat expansions.
Lingua originaleEnglish
pagine (da-a)2658.e1-2658.e1-5
RivistaNeurobiology of Aging
Volume35
DOI
Stato di pubblicazionePubblicato - 2014

Keywords

  • C9orf72
  • FTD
  • FTD-ALS
  • GRN
  • TMEM106B
  • rs1990622
  • rs3173615

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