The coding-synonymous polymorphism rs1045280 (Ser280Ser) in beta-arrestin 2 (ARRB2) gene is associated with tardive dyskinesia in Chinese patients with schizophrenia.
BACKGROUND
Tardive dyskinesia (TD) is a severe and potentially irreversible adverse effect of long-term antipsychotic treatment. Typical antipsychotics are commonly binding to the dopamine receptor D2 (DRD2), but the occurrence of antipsychotic-induced TD is rather delayed; therefore, the development of TD may be associated with mediators or signalling complexes behind DRD2, such as beta-arrestin 2 (ARRB2), an important mediator between DRD2 and serine-threonine protein kinase (AKT) signal cascade.


METHODS
A case-control study to evaluate the association between rs1045280 (Ser280Ser) and antipsychotic-induced TD was performed amongst 381 patients (TD/non-TD = 228/153).


RESULTS
There was a significant difference in the genotype distribution between TD and non-TD groups (P = 0.025); furthermore, the allelic analysis indicated that patients with T allele had increased risk of TD occurrence (OR(T) = 1.58, 95% CI = 1.14-2.19, P = 0.007).


CONCLUSIONS
To the best of our knowledge, this is the first study reporting a positive association between the SNP rs1045280 and TD in schizophrenic patients.
Liou
Y-J
YJ
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
Wang
Y-C
YC
Chen
J-Y
JY
Chen
M-L
ML
Chen
T-T
TT
Bai
Y-M
YM
Lin
C-C
CC
Liao
D-L
DL
Lai
I-C
IC
D014150:Antipsychotic Agents / Q000009:adverse effects*; D019390:Arrestins / Q000235:genetics*; D044466:Asian People; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004409:Dyskinesia, Drug-Induced / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D016366:Open Reading Frames / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013624:Taiwan; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
C000605254:ARRB2 protein, human; D014150:Antipsychotic Agents; D019390:Arrestins; D005819:Genetic Markers; D017448:Receptors, Dopamine D2; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D051057:Proto-Oncogene Proteins c-akt