Influence of DRD2 and ANKK1 genotypes on apomorphine-induced growth hormone (GH) response in alcohol-dependent patients.
BACKGROUND
D(2) 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 D(2) 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.


CONCLUSIONS
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 D(2) receptor availability and signal transduction in the dopaminergic pathways. Small sample size in our study limits the generalizability of our results.
Lucht
Michael
M
Hospital for Psychiatry and Psychotherapy, Ernst Moritz Arndt University Greifswald, Germany.
Samochowiec
Agnieszka
A
Samochowiec
Jerzy
J
Jasiewicz
Andrzej
A
Grabe
Hans Joergen
HJ
Geissler
Ingrid
I
Rimmbach
Christian
C
Rosskopf
Dieter
D
Grzywacz
Anna
A
Wysiecka
Justyna Pełka
JP
Tybura
Piotr
P
Brzuchalski
Bogusław
B
Bieńkowski
Przemysław
P
D000328:Adult; D000437:Alcoholism / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D000661:Amphetamine; D000704:Analysis of Variance; D019540:Area Under Curve; D019002:CD56 Antigen; D000697:Central Nervous System Stimulants; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019006:Neural Cell Adhesion Molecules / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D013997:Time Factors
D019002:CD56 Antigen; D000697:Central Nervous System Stimulants; C493593:DRD3 protein, human; C522918:NCAM1 protein, human; D019006:Neural Cell Adhesion Molecules; D050637:Receptors, Dopamine D3; D013006:Growth Hormone; D000661:Amphetamine; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases