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Genetic diagnostics of functional variants of the human dopamine D2 receptor gene

Doehring, Alexandra; Kirchhof, Anja; Lötsch, Jörn

doi: 10.1097/YPG.0b013e32832d0941
Original Articles

Introduction The importance of dopamine D2 receptors (DRD2) for central nervous dopaminergic signalling makes variants in the DRD2 gene potential modulators of the risk or course of various behavioural, psychiatric or neurologic diseases (e.g. addiction, schizophrenia, Parkinson's disease). We developed Pyrosequencing genetic screening assays for single nucleotide polymorphisms spanning the whole range of the DRD2 gene locus up to the functionally related ankyrin repeat and kinase domain containing 1 gene (ANKK1) located at approximately 10 kb downstream of DRD2.

Methods Assays for 11 genetic variants with reported functional association were developed in DNA samples from 300 unrelated healthy Caucasians and validated by independent conventional sequencing.

Results In all DNA samples the DRD2/ANKK1 genetic variants were identified correctly as verified by the control samples. The observed frequencies of homozygous, heterozygous and noncarriers of the minor alleles were in agreement with the Hardy–Weinberg equilibrium. Observed minor allele frequencies were DRD2 rs12364283T>C: 6.5%, rs1799978A>G: 4.8%, rs1799732C del: 14.2%, rs4648317C>T: 12.8%, rs1079597G>A: 13.8%, rs1076560G>T: 14.5%, rs1800496C>T: 0.2%, rs1801028C>G: 3.0%, rs6275C>T: 32.7%, rs6277C>T: 53.0% and ANKK1 rs1800497C>T: 17.5%.

Conclusion The presently developed Pyrosequencing assays are provided to facilitate further research toward personalized approaches to pathophysiological conditions involving behavioural, psychiatric and neurologic disorders including addiction, schizophrenia and Parkinson's disease.

Pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany

Correspondence to Professor Jörn Lötsch, MD, Pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang Goethe-University, Theodor Stern Kai 7, Frankfurt am Main 60590, Germany

Tel: +49 69 6301 4589; fax: +49 69 6301 7636;


Received 24 November 2008 Revised 1 April 2009 Accepted 15 April 2009

© 2009 Lippincott Williams & Wilkins, Inc.