Adenosine A1 receptor and bipolar affective disorder: systematic screening of the gene and association studies

In the present study we sought to identify genetic variation in the adenosine A1 receptor (A1AR) gene on chromosome 1q31-32.1, which through alteration of protein function or level of expression might contribute to the genetic predisposition to bipolar affective disorder. We performed a systematic mutation scan of the whole coding sequence as well as 5' and 3' untranslated regions by means of single-strand conformation analysis. The region upstream to the coding sequence we investigated contains two functional promoters. Screening 42 patients with bipolar affective disorder, we detected 11 DNA sequence variants (48T/A, 267 + 275C/T, 805T/G, 1777C/A, 1827C/T, 1904C/T, 2126G/T, 2294insT, 2776C/T, 2777del36, 2819T/G). Determining the frequency of these variants in 42 anonymous blood donors, we observed a non-significant (P < 0.06) trend towards an underrepresentation of the 2126T variant in patients when compared to controls. On the other hand, the 2777del36 and the 2819G variant were not found among the controls. These findings were followed up in a large independent replication sample. However, we were not able to confirm the initial findings in the second sample. Our data suggest that genetically determined variation of the A1AR and its two promoters do not play a major role in the development of bipolar affective disorder.