CYP1A2 酶基因多态性与奥氮平治疗老年性痴呆精神行为症状疗效的关联性
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国家自然科学基金青年项目(81501154)


Association between polymorphisms of CYP1A2 gene and olanzapine in treating senile dementia patients with behavioral and psychological symptoms
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    摘要:

    目的 探讨细胞色素P450 1A2(CYP1A2)酶基因多态性与奥氮平治疗老年性痴呆患者精 神行为症状(BPSD)疗效的相关性。方法 入组57 例伴有严重BPSD 的老年性痴呆患者,给予奥氮平治 疗8 周,治疗前后测定神经精神问卷(NPI)以评定疗效、简易精神状态检查量表(MMSE)评定认知功能变 化,药物副反应量表(TESS)评定药物不良反应,同时测定体重、腹围、血压、血糖、糖化血红蛋白、血脂、 胆碱酯酶、血清胱抑素、血清垂体泌乳素等代谢相关指标及奥氮平血药浓度;采用荧光原位杂交技术检 测CYP1A2 酶基因C734A 多态性(AA 型、AC 型及CC 型)。结果 共有50 例患者完成研究。3 种基因型 NPI 患者总分及照料者总分评分在治疗结束后均显著下降,但3 种基因型之间的NPI 总评分减分差异均 无统计学意义。3 种基因型之间TESS 分值、认知功能、代谢相关不良反应及血药浓度差异亦无统计学 意义。结论 CYP1A2 酶基因多态性与奥氮平治疗老年性痴呆患者BPSD 的疗效无明显相关性。

    Abstract:

    Objective To investigate the relationship between polymorphism of cytochrome P450 (CYP) 1A2 gene and the efficacy of olanzapine in the treatment of senile dementia patients with behavioral and psychological symptoms of dementia( BPSD). Methods A total of 57 Alzheimer disease patients with severe BPSD were enrolled in the study and given olanzapine for eight weeks. The Neuropsychiatric Inventory( NPI) questionnaire was applied to evaluate the curative effect, Mini-mental State Examination ( MMSE) for cognition change, and Treatment Emergent Symptom Scale( TESS) for adverse drug reactions before and after treatment. At the same time, body weight, abdominal circumference, blood pressure, blood glucose, HbA1c, blood lipids, cholinesterase, serum cystatin, serum pituitary prolactin and other metabolites related indicators and olanzapine plasma concentration were measured. CYP1A2 gene polymorphism( AA, AC and CC type) was detected by fluorescence in situ hybridization( FISH). Results A total of 50 patients completed the study. The NPI total scores of patients and caregivers in three genotype groups decreased significantly after the treatment. However, there was no significant difference among the three genotypes in NPI total score. There was no significant difference in TESS score, cognitive function, metabolic-related side effects and plasma concentration among the three genotypes. Conclusions There was no significant association between CYP1A2 gene polymorphism and the efficacy of olanzapine treatment of senile dementia patients with BPSD.

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丁燕莉 徐韩 陈剑华. CYP1A2 酶基因多态性与奥氮平治疗老年性痴呆精神行为症状疗效的关联性[J].神经疾病与精神卫生,2018,18(3):
DOI :10.3969/j. issn.1009-6574.2018.03.001.

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  • 在线发布日期: 2018-08-21