Influence of TAAR6 polymorphisms on response to aripiprazole.
BACKGROUND
There is some evidence suggesting a role of TAAR6 in schizophrenia. The aim of the present study is to investigate possible influences of a panel of markers in TAAR6 (rs8192625, rs4305745, rs4305746, rs6903874, rs6937506) on clinical outcomes and side effects in a sample of Korean schizophrenic aripiprazole treated patients.


METHODS
Efficacy was assessed at baseline and weeks 1, 2, 4, 6, 8 using CGI-S, CGI-I, BPRS and SANS. Side effects were evaluated through SAS, BAS and AIMS. Multivariate analysis of covariance (MANCOVA) was used to test possible influences of single SNPs on clinical and safety scores. Tests for associations using multi-marker haplotypes were performed using the statistics environment "R".


RESULTS
A significant time per genotype interaction was found between rs4305746 in repeated measures of ANOVA on BPRS scores (F=2.45, df=10,365, p=0.008). In particular G/A and A/A genotype patients were more likely to improve over time as compared to carriers of the G/G genotype. Permutation analysis confirmed a significant effect of rs4305746 on course of BPRS scores over time (p=0.007). Haplotype analysis did not reveal any significant association with clinical and safety scores at any time.


CONCLUSIONS
A possible association could exist between some genotypes in TAAR6 and response to aripiprazole. However, several limitations characterize the present work, such as small sample size, the finding related to a single scale and the possibility of false positive findings, thus further investigation is required.
Institute of Psychiatry, University of Bologna, Bologna, Italy. alessandro.serretti@unibo.it
Alessandro
A
Serretti
Chi-Un
CU
Pae
Alberto
A
Chiesa
Laura
L
Mandelli
Diana
D
De Ronchi
D000328:Adult; D000068180:Aripiprazole; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000187:drug effects / Q000235:genetics; D005819:Genetic Markers / Q000187:drug effects / Q000235:genetics; D006239:Haplotypes / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide / Q000187:drug effects / Q000235:genetics*; D011446:Prospective Studies; D015363:Quinolones / Q000494:pharmacology* / Q000627:therapeutic use; D043562:Receptors, G-Protein-Coupled; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics; D000095383:Trace Amine-Associated Receptors
D000068180:Aripiprazole; D018797:Cell Cycle Proteins; D005819:Genetic Markers; D009687:Nuclear Proteins; D010879:Piperazines; D015363:Quinolones; D043562:Receptors, G-Protein-Coupled; C493988:TAAR6 protein, human; D000095383:Trace Amine-Associated Receptors