title: Human adenosine A2a receptor (A2aAR) gene: systematic mutation screening in patients with schizophrenia.
abstract: Several lines of evidence suggest an involvement of adenosine A2a receptor (A2aAR) mediated adenosinergic neuromodulation in the etiopathogenesis of schizophrenia. We therefore performed a systematic mutation scan of the complete coding region of the human A2aAR gene in a sample of 42 schizophrenic patients. We detected one rare naturally occurring receptor variant (Gly-340-Ser) and two silent mutations (405C/T and 1083C/T). To our knowledge the Gly-340-Ser substitution is the first naturally occurring molecular variant of the A2aAR identified. Determining the frequency of the three variants in 42 unrelated healthy controls, we observed a significant trend towards an overrepresentation of the 1083T variant in patients when compared to controls (p = 0.041). This trend was followed up in a large independent replication sample. However, we were not able to confirm the original trend in the second sample (p = 0.367). The Ser-340 variant was found in a single schizophrenic individual. Investigation of the patient's family revealed independent segregation between the Ser-340 variant and psychiatric illness. Our data suggest that genetically determined structural variation of the A2aAR does not play a major role in the development of schizophrenia.
authors.affiliation: Department of Psychiatry, Julius-Maximilians-University, Würzburg, Federal Republic of Germany.
authors.forename: J
authors.initials: J
authors.lastname: Deckert
authors.forename: M M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: M
authors.initials: M
authors.lastname: Rietschel
authors.forename: D
authors.initials: D
authors.lastname: Wildenauer
authors.forename: B
authors.initials: B
authors.lastname: Bondy
authors.forename: M A
authors.initials: MA
authors.lastname: Ertl
authors.forename: M
authors.initials: M
authors.lastname: Knapp
authors.forename: P R
authors.initials: PR
authors.lastname: Schofield
authors.forename: M
authors.initials: M
authors.lastname: Albus
authors.forename: W
authors.initials: W
authors.lastname: Maier
authors.forename: P
authors.initials: P
authors.lastname: Propping
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005820:Genetic Testing / Q000379:methods*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D018047:Receptors, Purinergic P1 / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D018047:Receptors, Purinergic P1