A genetic variation in the ADORA2A gene modifies age at onset in Huntington's disease

• Main Authors: 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
• Format: Article
• Language: English
• Published: Elsevier 2009-09-01
• Series: Neurobiology of Disease
• Subjects: Huntington's disease; A2A receptors; Polymorphism
• Online Access: http://www.sciencedirect.com/science/article/pii/S096999610900165X
• ISSN: 1095-953X

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.