Systematic mutation screening and association study of the A₁ and A_2a adenosine receptor genes in panic disorder suggest a contribution of the A_2a gene to the development of disease

Abstract

Several lines of evidence suggest a contribution of adenosinergic neurotransmission to the development of panic disorder. We therefore hypothesized that variation in the A₁ and A_2a adenosine receptor (AR) genes modifies genetic susceptibility to panic disorder. To test this hypothesis, we screened 38 patients with panic disorder for mutations in the coding sequence of the A₁AR and A_2aAR genes. An association study between the identified DNA sequence variants and panic disorder was performed in an extended sample of 89 patients and matched controls. One silent mutation (716T/G) in the A₁AR gene and two silent mutations (432C/T and 1083C/T) in the A_2aAR gene were detected. The association sample shows a significant association between the 1083T allele (P = 0.01) and 1083T/T genotype (P = 0.024) of the A_2AR gene and panic disorder. Our findings thus lend further support to the hypothesis that the A_2aAR gene, or a locus in linkage disequilibrium with it, confers susceptibility to panic disorder. Replication studies in independent samples with nuclear families applying the transmission disequilibrium test (TDT) are warranted.