Exploratory study on association of genetic variation in TBC1D1 with antipsychotic-induced weight gain.
BACKGROUND
Previous studies have shown that antipsychotics with high propensity for antipsychotic-induced weight gain (AIWG) influence glucose transporter type 4 (GLUT4) mediated glucose intake. Variation in the gene encoding TBC1 domain family member 1 (TBC1D1), a Rab-GTPase activating protein regulating GLUT4 trafficking, has been associated with obesity. Therefore, we investigated the impact of TBC1D1 polymorphisms on AIWG.


METHODS
We analyzed rs9852 and rs35859249 in TBC1D1 in 195 schizophrenia subjects treated mostly with clozapine or olanzapine for up to 14 weeks. Association was tested using analysis of variance and analysis of covariance with change (%) from baseline weight as the dependent variable.


RESULTS
Analysis of covariance showed a non-significant trend for lower weight gain in carriers of the T-allele of rs9852 than in C-allele homozygotes (p = 0.063). This effect was more pronounced in the subgroup of patients treated with clozapine or olanzapine (p = 0.024). For rs35859249, no significant association with AIWG could be detected.


CONCLUSIONS
This is the first study examining the association between TBC1D1 and AIWG. The moderate association of rs9852, located in the 3'UTR near a miRNA binding site, indicates an influence of TBC1D1 on AIWG. Further investigations remain necessary to elucidate the role of this gene in AIWG.
Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Eva J
EJ
Brandl
Arun K
AK
Tiwari
Tristram A
TA
Lett
Sajid A
SA
Shaikh
Jeffrey A
JA
Lieberman
Herbert Y
HY
Meltzer
James L
JL
Kennedy
Daniel J
DJ
Müller
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D056726:Genetic Association Studies / Q000379:methods; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics*; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics*
D014150:Antipsychotic Agents; D020690:GTPase-Activating Proteins; C526441:TBC1D1 protein, human