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

作者：Dhaenens Claire Marie; Burnouf Sylvie; Simonin Clemence; Van Brussel Edwige; Duhamel Alain; Defebvre Luc; Duru Cecile; Vuillaume Isabelle; Cazeneuve Cecile; Charles Perrine; Maison Patrick; Debruxelles Sabrina; Verny Christophe; Gervais Helene; Azulay Jean Philippe; Tranchant Christine; Bachoud Levi Anne Catherine; Duerr Alexandra; Buee Luc; Krystkowiak Pierre; Sablonniere Bernard; Blum David^*

来源：Neurobiology of Disease, 2009, 35(3): 474-476.

DOI：10.1016/j.nbd.2009.06.009

• Huntington's disease
• A(2A) receptors
• Polymorphism

Based on the pathophysiological role of adenosine A(2A) 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 R(2) 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 A(2A) receptors in Huntington's disease.

• 出版日期2009-9