Abstract
Objective
To determine whether genetic polymorphisms related to pharmacodynamics with metabolic adverse effects, namely leptin promoter (LEP) rs7799039, leptin receptor rs1137101, dopamine D2 rs4436578, serotonin 5-HT2A rs6313, and serotonin 5-HT2C rs518147 and rs12836771, are associated with hyperglycemia induced by risperidone or clozapine in adult Thai patients with psychosis.
Methods
A total of 180 patients treated with risperidone-based (n=130) or clozapine-based (n=50) regimens were included in this study. Blood samples were analyzed for genotyping of the candidate genes and biochemical testing. Genotyping was performed by conducting a TaqMan real-time polymerase chain reaction-based analysis.
Results
The prevalence of hyperglycemia was higher in patients receiving clozapine (64.0%) than in those receiving risperidone (30.8%). Among the candidate genes, only the LEP rs7799039 polymorphism demonstrated a significant association with hyperglycemia (χ2=9.879, P=0.008) in patients treated with risperidone; patients with the AA genotype had the highest risk (41.1%), followed by those with AG (20.8%) and GG (0%) genotypes. Using the recessive genetic model (AA vs AG + GG), the odds ratio and 95% CI were 3.28 and 1.44 −7.50, respectively. None of the genes were associated with hyperglycemia in patients treated with clozapine. A binary logistic regression revealed that the LEP rs7799039 polymorphism demonstrated a significant association with hyperglycemia, independent of body-mass index (BMI) in patients receiving risperidone; the odds ratio (95% CI) was 3.188 (1.399–7.262), P=0.006. By contrast, none of the pharmacodynamic genetic factors, except for BMI, were significantly associated with hyperglycemia in patients receiving clozapine.
Conclusion
The risk of type 2 diabetes mellitus is associated with the LEP rs7799039 polymorphism in Thai adults receiving risperidone but not in those receiving clozapine. Clarifying underlying mechanisms and risk of hyperglycemia provides an opportunity to prevent impaired glucose metabolism in patients receiving risperidone or clozapine.
Acknowledgments
The authors gratefully acknowledge the staff of Somdet Chaopraya Institute of Psychiatry in central Thailand and Jirapa Kerdmongkol at the Department of Pathology, Ramathibodi Hospital, Mahidol University for their assistance. The authors wish to thank all the patients who took part in this study. This work was supported by Mahidol University.
Ethics approval and consent to participate
The study protocol was reviewed and approved by the ethics committee of Ramathibodi Hospital (Approval reference number ID MURA2015/23). All methods were carried out in accordance with the Declaration of Helsinki.
Author contributions
All the authors participated in the interpretation and the review of the data. PS, AP and WU designed the study. PS, AP, WU, NJ, SP and CNN conducted the data retrieval and analyzed the data. PS, AP, SV and MHK wrote the manuscript. PS, AP, CS and MHK gave constructive suggestions during the preparation of the manuscript. All the authors also participated in the revision of the manuscript and read and approved the final manuscript. All authors agree to be accountable for all aspects of the work.
Disclosure
The abstract of this paper was presented at the 70th AACC Annual Scientific Meeting as a poster presentation with interim findings. The poster’s abstract was published in “Abstract Guide” in poster sessions: Endocrinology/Hormones. All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.