Bishop Jeffrey R, Ellingrod Vicki L, Moline Jessica, Miller Del
Department of Pharmacy Practice, College of Pharmacy, University of Illinois, Chicago, IL, USA.
Med Sci Monit. 2006 Feb;12(2):BR47-50. Epub 2006 Jan 26.
Despite advances in schizophrenia treatment, nearly 30% of patients do not respond to atypical antipsychotic agents, such as olanzapine. Furthermore, 30-60% of patients will gain significant weight during the course of olanzapine therapy. Little research has been done to investigate the relationship between antipsychotic treatment outcomes and genetic variability in second messengers coupled to serotonin (5HT) receptors. The purpose of this investigation was examine associations between the second messenger G-Protein Beta3 Subunit Gene (GNB3) C825T polymorphism and olanzapine response and weight gain treatment.
MATERIAL/METHODS: We conducted a pharmacogenetic association study to examine GNB3 genotypes in relation to olanzapine clinical response (as measured by the Brief Psychiatric Rating Scale or Scale for the Assessment of Negative Symptoms) or weight gain. Subjects included forty-two individuals meeting DSM-IV criteria for schizophrenia that started olanzapine, were titrated to a fixed dose for 6 weeks, and subsequently genotyped for this investigation.
No statistically significant associations existed between our outcome variables and GNB3 genotypes. However we did observe trends suggesting a potential relationship between the TT genotype, response, and weight gain that warrant further investigation.
Preliminary results showed no statistical relationship between the C825T polymorphism and olanzapine response or weight gain. Numerical differences in outcome measures between the TT vs. CT/CC genotype groups indicate that G-protein second messenger systems variability coupled to primary targets of atypical antipsychotics may relate to clinical outcomes in persons with schizophrenia and that future research in this area is warranted.
尽管精神分裂症治疗取得了进展，但近30%的患者对非典型抗精神病药物（如奥氮平）无反应。此外，30 - 60%的患者在奥氮平治疗过程中会显著增重。关于抗精神病治疗结果与与5-羟色胺（5HT）受体偶联的第二信使基因变异性之间的关系，目前研究较少。本研究的目的是探讨第二信使G蛋白β3亚基基因（GNB3）C825T多态性与奥氮平反应及体重增加治疗之间的关联。
材料/方法：我们进行了一项药物遗传学关联研究，以检查GNB3基因型与奥氮平临床反应（通过简明精神病评定量表或阴性症状评定量表测量）或体重增加之间的关系。研究对象包括42名符合DSM-IV精神分裂症标准且开始使用奥氮平治疗的患者，这些患者经滴定至固定剂量并持续6周，随后进行基因分型以供本研究使用。
我们的结果变量与GNB3基因型之间不存在统计学上的显著关联。然而，我们确实观察到一些趋势，表明TT基因型、反应和体重增加之间可能存在潜在关系，值得进一步研究。
初步结果显示C825T多态性与奥氮平反应或体重增加之间无统计学关系。TT基因型组与CT/CC基因型组在结果测量上的数值差异表明，与非典型抗精神病药物主要靶点偶联的G蛋白第二信使系统变异性可能与精神分裂症患者的临床结果有关，该领域未来的研究很有必要。
