Replication of SULT4A1-1 as a Pharmacogenetic Marker of Olanzapine Response and Evidence of Lower Weight Gain in the High Response Group

Abstract

Aim: Antipsychotic efficacy biomarkers have the potential to improve outcomes in psychotic patients. This study examined the effect of SULT4A1-1 haplotype status (rs2285162 [A]-rs2285167 [G]) on olanzapine response. Patients & methods: We evaluated 87 olanzapine treated subjects from Phases 1, 1B and 2 of the CATIE trial for the impact of SULT4A1-1 status on change in Positive and Negative Syndrome Scale (PANSS) total score using two models of response. We also examined weight change. Results: SULT4A1-1-positive status correlated with superior olanzapine response in Phase 1 (p = 0.004 for model 1 and p = 0.001 for model 2) and Phases 1B/2 (p = 0.05 for model 1 and p = 0.007 for model 2). SULT4A1-1-positive subjects gained significantly less weight per month on olanzapine, 0.15 lbs, than did SULT4A1-1-negative subjects, 2.27 lbs (p = 0.04). Conclusion: This study provides a second replication of superior olanzapine response in SULT4A1-1-positive subjects compared with SULT4A1-1-negative subjects. SULT4A1-1-positive subjects treated with olanzapine also gained less weight than SULT4A1-1-negative subjects.

Original submitted 19 December 2013; Revision submitted 17 March 2014

Keywords::

• antipsychotic response
• biomarker
• CATIE trial
• weight gain

Financial & competing interests disclosure

MD Brennan and TL Ramsey are equity holders of SureGene, LLC. This work was supported by National Institutes of Mental Health grant MH078437 to MD Brennan. The principal investigators of the CATIE trial were JA Lieberman, TS Stroup and JP McEvoy. The CATIE trial was funded by a grant from the National Institute of Mental Health (N01 MH900001) along with MH074027 (principal investigator: PF Sullivan). Prior genotyping expenses for the CATIE study was funded by Eli Lilly and Company. The funding sources had no input into the design of the study or the writing of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined inthe Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

MD Brennan and TL Ramsey are equity holders of SureGene, LLC. This work was supported by National Institutes of Mental Health grant MH078437 to MD Brennan. The principal investigators of the CATIE trial were JA Lieberman, TS Stroup and JP McEvoy. The CATIE trial was funded by a grant from the National Institute of Mental Health (N01 MH900001) along with MH074027 (principal investigator: PF Sullivan). Prior genotyping expenses for the CATIE study was funded by Eli Lilly and Company. The funding sources had no input into the design of the study or the writing of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.