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Influence of DRD2 and ANKK1 genotypes on apomorphine-induced growth hormone (GH) response in alcohol-dependent patients
Authors:Michael Lucht  Agnieszka Samochowiec  Jerzy Samochowiec  Andrzej Jasiewicz  Hans Joergen Grabe  Ingrid Geissler  Christian Rimmbach  Dieter Rosskopf  Anna Grzywacz  Justyna Pełka Wysiecka  Piotr Tybura  Bogusław Brzuchalski  Przemysław Bieńkowski
Affiliation:1. Hospital for Psychiatry and Psychotherapy, Ernst Moritz Arndt University Greifswald, Germany;2. Department of Psychiatry, Pomeranian Medical University, Szczecin, Poland;3. MSKP University of Szczecin, Szczecin, Poland;4. Institute of Pharmacology, Ernst Moritz Arndt University Greifswald, Germany;5. Department of Pharmacology, Institute of Psychiatry and Neurology, Warsaw, Poland
Abstract:

Background

D2 receptor function can be assessed by growth hormone (GH) response to apomorphine. Several association studies between dopamine receptor polymorphisms and results of the apomorphine challenge test with normal and alcohol-dependent subjects yielded inconsistent results. In this pilot study, we tested polymorphisms from the DRD2 region for GH response to apomorphine challenge in more detail.

Methods

Apomorphine challenge tests measuring GH responses on 5 time points were performed on day 1 of alcohol detoxification in 43 patients with alcohol dependence; patients were genotyped for 11 polymorphisms including DRD2, ANKK1, NCAM1 and TTC12.

Results

Associations (p < 0.05) were found for ANKK1 (rs11604671, rs1800497) and DRD2 (rs6276, rs1076560), which are located on adjacent chromosomal positions. Consistent with PET studies suggesting a reduced D2 receptor availability in patients carrying the ANKK1 rs1800497 T polymorphism (formerly known as DRD2 TaqI A1) we found a reduced GH response to apomorphine in those subjects.

Conclusion

This has been the first study showing significant associations between apomorphine-induced GH response and SNPs in DRD2 and ANKK1 in alcohol-dependent patients. In this respect, our preliminary results are in line with other reports which suggested that DRD2 and ANKK1 polymorphisms influence D2 receptor availability and signal transduction in the dopaminergic pathways. Small sample size in our study limits the generalizability of our results.
Keywords:A, Adenine   ANKK1, Ankyrin repeat and kinase domain containing 1   ANOVA, Analysis of variance   AUC, Areas under the curie   bp, Base pair   C, Cytosine   CIWA, Clinical Institute Withdrawal Assessment for Alcohol   COGA, Collaborative Studies on Genetics of Alcoholism   del, Deletion   DRD2, Dopamine receptor D2   G, Guanine   GH, Growth hormone   Glu, Glutamyl   ins, Insertion   L-DOPA, L-3,4-dihydroxyphenylalanine   Lys, Lysyl   NCAM1, Neural cell adhesion molecule 1   NF-kappaB, Nuclear factor kappa-light-chain-enhancer of activated B cells   PCR, Polymerase chain reaction   PET, Positron emission tomography   RFLP, Restriction fragment length polymorphism   SEM, Standard error of the mean   SNP, Single nucleotide polymorphism   SPSS, Statistical Package for the Social Sciences   T, Thymine   TTC12, Tetratricopeptide repeat domain 12
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