SYSTEMATIC MUTATION SCREENING AND ASSOCIATION STUDY OF THE A(1) AND A(2A) ADENOSINE RECEPTOR GENES IN PANIC DISORDER SUGGEST A CONTRIBUTIONOF THE A(2A) GENE TO THE DEVELOPMENT OF DISEASE

Several lines of evidence suggest a contribution of adenosinergic neur otransmission to the development of panic disorder. We therefore hypot hesized that variation in the A(1) and A(2a) adenosine receptor (AR) g enes modifies genetic susceptibility to panic disorder. To test this h ypothesis, we screened 38 patients with panic disorder for mutations i n the coding sequence of the A(1)AR and A(2a)AR genes. An association study between the identified DNA sequence variants and panic disorder was performed in an extended sample of 89 patients and matched control s. One silent mutation (716T/G) in the A(1)AR gene and two silent muta tions (432C/T and 1083C/T) in the A(2a)AR gene were detected. The asso ciation sample shows a significant association between the 1083T allel e (P=0.01) and 1083T/T genotype (P=0.024) of the A(2A)R gene and panic disorder. Our findings thus lend further support to the hypothesis th at the A(2a)AR gene, or a locus in linkage disequilibrium with it, con fers susceptibility to panic disorder. Replication studies in independ ent samples with nuclear families applying the transmission disequilib rium test (TDT) are warranted.