Aquaporin 4及MAOA基因對使用Olanzapine, Risperidone及Paliperidone的精神分裂症患者的影響

Different Impacts of Aquaporin 4 and MAOA Allele Variation Among Olanzapine, Risperidone, and Paliperidone in Schizophrenia

鍾廷聖(Ting-Sheng Chung)

指導教授 ： 紀宗呈

長榮大學/健康科學學院/醫學研究所/碩士(2012年)

https://doi.org/10.6833/CJCU.2012.00220

摘要

背景:神經細胞凋萎被認為與精神分裂症有密切相關；而之前的研究發現在神經細胞凋萎之前，神經細胞膜上的水通道會有調節的情形。在身體的許多器官中，皆有水通道的存在。而在所有的水通道中，只有aquaporin 4 (AQP4)在大腦中會高度表現，而且被認為在神經系統的環境中扮演相當重要的角色。在本研究中，我們欲探討三種抗精神病劑olanzapine, risperidone, 及paliperidone的藥物劑量及臨床反應與AQP4及MAOA (Monoamine oxidase A)基因的相關性。
方法：我們納入了91位精神分裂症患者，被隨機分配服用olanzapine (共44位), risperidone (共23位), or paliperidone (共24位)三種抗精神病劑，並在所有的患者中，分析其AQP4 and MAOA的基因型。
結果：當個案為AQP4 non-C polymorphism，其olanzapine所需的治療劑量會比較高 (χ2= 4.163, P = 0.041)。個案若為短型的MAOA polymorphism，在治療上則需要較高的risperidone劑量(χ2= 5.124, P = 0.024)。個案若為吸煙者（目前有吸煙或曾經抽過100隻以上的煙）同樣也需要較高劑量的olanzapine來治療(χ2= 4.905, P = 0.027)。
結論：AQP4的基因基會影響個案所需olanzapine劑量；然而，在血腦屏障中AQP4所扮演的角色仍需進一步的研究。

關鍵字

精神分裂症

並列摘要

Background: Apoptosis has been considered to be involved in schizophrenia. Water channels are modulated just prior to apoptosis. In the aquaporin family, aquaporin 4 (AQP4) is most highly expressed in the brain, and is supposed to play an important role in a neuronal environment. In this clinical study, we investigated the relationship between the AQP4 polymorphism and drug response in schizophrenia under the control of the MAOA (Monoamine oxidase A) promoter gene.
Methods: We recruited 91 patients with schizophrenia, and they were randomized to received olanzapine (numbers: 44), risperidone (numbers: 23), or paliperidone (numbers: 24). Genotyping of AQP4 and MAOA polymorphisms was done in all patients.
Results: Patients with the AQP4 non-C polymorphism needed a higher dosage of olanzapine for treatment (z= 4.163, P = 0.041), and patients with a short form of the MAOA polymorphism needed a higher dosage of risperidone for treatment (z= 5.124, P = 0.024). Patients who smoked cigarettes needed a higher dosage of olanzapine for treatment (z= 4.905, P = 0.027), but cigarette smoking did not affect the dosage of paliperidone.
Conclusions: The AQP4 polymorphism may have an effect in influencing the dosage of olanzapine. However, the role of AQP4 polymorphisms in blood-brain barrier and different neuroprotective effects need further exploration in future study.

並列關鍵字

Apoptosis ； Aquaporin 4 ； Monoamine oxidase A

參考文獻

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