BACKGROUND Use of the antipsychotic drug olanzapine by patients with schizophrenia is associated with autonomic nervous system (ANS) dysfunction. It is presumed that there are interindividual differences in ANS dysfunction that correspond to pharmacogenetics. In this study, we investigated whether genetic polymorphisms in ABCB1, CYP1A2, and UGT1A4 are associated with this observed ANS dysfunction. METHODS A total of 91 schizophrenia patients treated with olanzapine monotherapy participated in this study. A power spectral analysis of heart rate variability was used to assess ANS activity. The TaqMan system was used to genotype seven single nucleotide polymorphisms (SNPs) in CYP1A2 (rs2069514 and rs762551), UGT1A4 (rs2011425), and ABCB1 (rs1045642, rs1128503, rs2032582, rs2235048). RESULTS Sympathetic nervous activity was significantly higher in individuals with the UGT1A4 rs2011425 G allele than in those with the UGT1A4 rs2011425 non-G allele (sympathetic activity, p = .001). Furthermore, sympathetic nervous activity was also significantly associated with UGT1A4 rs2011425 genotype as revealed by multiple regression analysis (sympathetic activity, p = .008). CONCLUSIONS We suggest that the UGT1A4 rs2011425 polymorphism affects olanzapine tolerability because it is associated with the observed side effects of olanzapine in schizophrenia patients, namely sympathetic dysfunction.

中文翻译：

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CYP1A2，UGT1A4和ABCB1基因多态性与奥氮平治疗的精神分裂症患者的自主神经系统功能障碍相关。

背景技术精神分裂症患者使用抗精神病药物奥氮平与植物神经系统功能障碍有关。据推测，ANS功能障碍存在个体差异，这与药物遗传学相对应。在这项研究中，我们调查了ABCB1，CYP1A2和UGT1A4的遗传多态性是否与这一观察到的ANS功能障碍有关。方法总共91例奥氮平单药治疗的精神分裂症患者参加了这项研究。心率变异性的功率谱分析用于评估ANS活动。TaqMan系统用于对CYP1A2（rs2069514和rs762551），UGT1A4（rs2011425）和ABCB1（rs1045642，rs1128503，rs2032582，rs2235048）中的七个单核苷酸多态性（SNP）进行基因分型。结果UGT1A4 rs2011425 G等位基因个体的交感神经活动明显高于UGT1A4 rs2011425非G等位基因的个体（交感神经活动，p = 0.001）。此外，如多元回归分析所揭示，交感神经活动也与UGT1A4 rs2011425基因型显着相关（交感活动，p = 0.008）。结论我们建议UGT1A4 rs2011425基因多态性影响奥氮平的耐受性，因为它与奥氮平在精神分裂症患者中观察到的副作用有关，即交感神经功能障碍。多元回归分析显示，交感神经活动也与UGT1A4 rs2011425基因型显着相关（交感活动，p = .008）。结论我们建议UGT1A4 rs2011425基因多态性影响奥氮平的耐受性，因为它与奥氮平在精神分裂症患者中观察到的副作用有关，即交感神经功能障碍。多元回归分析显示，交感神经活动也与UGT1A4 rs2011425基因型显着相关（交感活动，p = .008）。结论我们建议UGT1A4 rs2011425基因多态性影响奥氮平的耐受性，因为它与奥氮平在精神分裂症患者中观察到的副作用有关，即交感神经功能障碍。