Neurobiology of Disease (Sep 2009)
A genetic variation in the ADORA2A gene modifies age at onset in Huntington's disease
- Claire-Marie Dhaenens,
- Sylvie Burnouf,
- Clémence Simonin,
- Edwige Van Brussel,
- Alain Duhamel,
- Luc Defebvre,
- Cécile Duru,
- Isabelle Vuillaume,
- Cécile Cazeneuve,
- Perrine Charles,
- Patrick Maison,
- Sabrina Debruxelles,
- Christophe Verny,
- Hélène Gervais,
- Jean-Philippe Azulay,
- Christine Tranchant,
- Anne-Catherine Bachoud-Levi,
- Alexandra Dürr,
- Luc Buée,
- Pierre Krystkowiak,
- Bernard Sablonnière,
- David Blum
Affiliations
- Claire-Marie Dhaenens
- Inserm, U837, Lille, France; Université Lille-Nord de France, USDL, IMPRT, Jean-Pierre Aubert Research Centre, Lille, France; Service de Neurologie et Pathologie du Mouvement, EA 2683, IMPRT, CHRU, Lille, France
- Sylvie Burnouf
- Inserm, U837, Lille, France; Université Lille-Nord de France, USDL, IMPRT, Jean-Pierre Aubert Research Centre, Lille, France
- Clémence Simonin
- Service de Neurologie et Pathologie du Mouvement, EA 2683, IMPRT, CHRU, Lille, France
- Edwige Van Brussel
- Inserm, U837, Lille, France; Université Lille-Nord de France, USDL, IMPRT, Jean-Pierre Aubert Research Centre, Lille, France
- Alain Duhamel
- CERIM, CHRU, Lille, France
- Luc Defebvre
- Service de Neurologie et Pathologie du Mouvement, EA 2683, IMPRT, CHRU, Lille, France
- Cécile Duru
- Service de Neurologie, UMR CNRS 8160, CHU, Amiens University Hospital, Amiens, France
- Isabelle Vuillaume
- Inserm, U837, Lille, France; Université Lille-Nord de France, USDL, IMPRT, Jean-Pierre Aubert Research Centre, Lille, France; UF Neurobiologie, Centre de Biologie Pathologie, CHRU Lille, France
- Cécile Cazeneuve
- AP-HP, Departement de Genetique et Cytogenetique, Groupe Hospitalier Pitie-Salpetriere, Paris, France
- Perrine Charles
- AP-HP, Departement de Genetique et Cytogenetique, Groupe Hospitalier Pitie-Salpetriere, Paris, France; AP-HP, Centre de référence maladie rare/maladie de Huntington, Créteil and Paris, France
- Patrick Maison
- AP-HP, Centre de référence maladie rare/maladie de Huntington, Créteil and Paris, France
- Sabrina Debruxelles
- CHU Bordeaux, Fédération de neurosciences cliniques et service de génétique médicale, Hôpital Pellegrin, Bordeaux, France
- Christophe Verny
- Département de Neurologie, CHU, Angers, France
- Hélène Gervais
- Service de Neurologie, Hôpital Pierre Wertheimer, Lyon-Bron, France
- Jean-Philippe Azulay
- Service de Neurologie et pathologie du mouvement, hôpital de la Timone, Marseille, France
- Christine Tranchant
- Service de Neurologie, Hôpital Civil, Strasbourg, France
- Anne-Catherine Bachoud-Levi
- AP-HP, Centre de référence maladie rare/maladie de Huntington, Créteil and Paris, France
- Alexandra Dürr
- AP-HP, Departement de Genetique et Cytogenetique, Groupe Hospitalier Pitie-Salpetriere, Paris, France; AP-HP, Centre de référence maladie rare/maladie de Huntington, Créteil and Paris, France; Inserm, UMR-S679, Paris, France
- Luc Buée
- Inserm, U837, Lille, France; Université Lille-Nord de France, USDL, IMPRT, Jean-Pierre Aubert Research Centre, Lille, France
- Pierre Krystkowiak
- AP-HP, Departement de Genetique et Cytogenetique, Groupe Hospitalier Pitie-Salpetriere, Paris, France
- Bernard Sablonnière
- Inserm, U837, Lille, France; Université Lille-Nord de France, USDL, IMPRT, Jean-Pierre Aubert Research Centre, Lille, France; UF Neurobiologie, Centre de Biologie Pathologie, CHRU Lille, France
- David Blum
- Inserm, U837, Lille, France; Université Lille-Nord de France, USDL, IMPRT, Jean-Pierre Aubert Research Centre, Lille, France; Corresponding author. Inserm, U837, Jean-Pierre Aubert Research Centre, 1 place de Verdun, 59045 Lille Cedex, France. Fax: +33320538562.
- Journal volume & issue
-
Vol. 35,
no. 3
pp. 474 – 476
Abstract
Based on the pathophysiological role of adenosine A2A receptors in HD, we have evaluated the association of the 1976C/T single-nucleotide polymorphism in the ADORA2A gene (rs5751876) with residual age at onset (AAO) in HD. The study population consisted of 791 unrelated patients belonging to the Huntington French Speaking Network. The variability in AAO attributable to the CAG repeats number was calculated by linear regression using the log (AAO) as the dependent variable, and the respective rs5751876 genotypes as independent variables. We show that the rs5751876 variant significantly influences the variability in AAO. The R2 statistic rose slightly but significantly (p=0.019) when rs5751876 T/T genotype was added to the regression model. Patients harbouring T/T genotype have an earlier AAO of 3.8 years as compared to C/C genotype (p=0.02). Our data thus strengthens the pathophysiological role of A2A receptors in Huntington's disease.
