A genetic variation in the ADORA2A gene modifies age at onset in Huntington's disease.
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.
Dhaenens
Claire-Marie
CM
Inserm, U837, Université Lille-Nord de France, USDL, IMPRT, Jean-Pierre Aubert Research Centre, Lille, France.
Burnouf
Sylvie
S
Simonin
Clémence
C
Van Brussel
Edwige
E
Duhamel
Alain
A
Defebvre
Luc
L
Duru
Cécile
C
Vuillaume
Isabelle
I
Cazeneuve
Cécile
C
Charles
Perrine
P
Maison
Patrick
P
Debruxelles
Sabrina
S
Verny
Christophe
C
Gervais
Hélène
H
Azulay
Jean-Philippe
JP
Tranchant
Christine
C
Bachoud-Levi
Anne-Catherine
AC
Dürr
Alexandra
A
Buée
Luc
L
Krystkowiak
Pierre
P
Sablonnière
Bernard
B
Blum
David
D
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002648:Child; D015331:Cohort Studies; D005838:Genotype; D006801:Humans; D006816:Huntington Disease / Q000453:epidemiology* / Q000235:genetics*; D016014:Linear Models; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043705:Receptor, Adenosine A2A / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion; D055815:Young Adult
D043705:Receptor, Adenosine A2A