Association Between Polymorphisms of and Genes and Risperidone- or Clozapine-induced Hyperglycemia

Overview

Journal Pharmgenomics Pers Med

Publisher Dove Medical Press

Date 2019 Sep 10

PMID 31496784

Citations 3

Authors

Apichaya Puangpetch

Pornpen Srisawasdi

Weerapon Unaharassamee

Napa Jiratjintana

Somlak Vanavanan

Suweejuk Punprasit

Chalitpon Na Nakorn

Chonlaphat Sukasem

Martin H Kroll

Affiliations

Soon will be listed here.

Abstract

Objective: To determine whether genetic polymorphisms related to pharmacodynamics with metabolic adverse effects, namely leptin promoter () 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 (=130) or clozapine-based (=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 rs7799039 polymorphism demonstrated a significant association with hyperglycemia (χ=9.879, =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 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), =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 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.

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