Puangpetch Apichaya, Srisawasdi Pornpen, Unaharassamee Weerapon, Jiratjintana Napa, Vanavanan Somlak, Punprasit Suweejuk, Na Nakorn Chalitpon, Sukasem Chonlaphat, Kroll Martin H
Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Division of Clinical Chemistry, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Pharmgenomics Pers Med. 2019 Aug 6;12:155-166. doi: 10.2147/PGPM.S210770. eCollection 2019.
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.
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.
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.
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.
确定与有代谢不良反应的药效学相关的基因多态性，即瘦素启动子（）rs7799039、瘦素受体rs1137101、多巴胺D2 rs4436578、血清素5-HT2A rs6313以及血清素5-HT2C rs518147和rs12836771，是否与成年泰国精神病患者中由利培酮或氯氮平诱发的高血糖相关。
本研究纳入了总共180例接受基于利培酮（n = 130）或氯氮平（n = 50）方案治疗的患者。采集血样进行候选基因的基因分型和生化检测。基因分型通过基于TaqMan实时聚合酶链反应的分析进行。
接受氯氮平治疗的患者中高血糖的患病率（64.0%）高于接受利培酮治疗的患者（30.8%）。在候选基因中，仅rs7799039多态性在接受利培酮治疗的患者中显示出与高血糖有显著关联（χ² = 9.879，P = 0.008）；AA基因型的患者风险最高（41.1%），其次是AG基因型（20.8%）和GG基因型（0%）的患者。采用隐性遗传模型（AA与AG + GG比较），比值比和95%置信区间分别为3.28和1.44 - 7.50。在接受氯氮平治疗的患者中，没有基因与高血糖相关。二元逻辑回归显示，rs7799039多态性在接受利培酮治疗的患者中显示出与高血糖有显著关联，且独立于体重指数（BMI）；比值比（95%置信区间）为3.188（1.399 - 7.262），P = 0.006。相比之下，在接受氯氮平治疗的患者中，除BMI外，没有药效学遗传因素与高血糖显著相关。
2型糖尿病风险与接受利培酮治疗的泰国成年人中的rs7799039多态性相关，但与接受氯氮平治疗的患者无关。阐明高血糖的潜在机制和风险为预防接受利培酮或氯氮平治疗的患者葡萄糖代谢受损提供了机会。
