2023 年第 8 期 第 18 卷

单胺氧化酶A基因多态性与急性脑卒中后抑郁及奥氮平疗效的相关性分析

Relationship of monoamine oxidase A gene polymorphism with depression after acute stroke and therapeutic effect of olanzapine

作者：李波兰1孔焕育2贺巍1

英文作者：Li Bolan1 Kong Huanyu2 He Wei1

单位：1南方医科大学珠江医院药剂科，广州510280；2北京赛赋医药研究院有限公司，北京102600

英文单位：1Department of Pharmacy Zhujiang Hospital of Southern Medical University Guangzhou 510280 China; 2Beijing Saifu Pharmaceutical Research Institute Co. LTD. Beijing 102600 China

关键词：单胺氧化酶A基因多态性；急性脑卒中后抑郁；奥氮平

英文关键词：MonoamineoxidaseAgenepolymorphism;Depressionafteracutestroke;Olanzapine

• 摘要：

• 目的 探讨单胺氧化酶A（MAOA）基因多态性与急性脑卒中后抑郁及奥氮平疗效的相关性。方法 回顾性选取2020年9月至2022年9月南方医科大学珠江医院收治的172例急性脑卒中患者作为研究对象，根据汉密尔顿抑郁量表（HAMD）评分将患者分为抑郁组（HAMD评分≥8分，76例）和非抑郁组（HAMD评分＜8分，96例），抑郁组患者均接受奥氮平口服治疗。检测所有患者MAOA串联重复序列（MAOA-uVNTR）基因型及等位基因分布，收集一般资料、治疗前HAMD评分、美国国立卫生研究院卒中量表（NIHSS）评分和日常生活能力量表（ADL）评分以及抑郁组患者治疗后的各项评分。使用多因素Logistic回归模型分析急性脑卒中后抑郁的影响因素、MAOA基因多态性与影响因素的交互作用及不同基因型与奥氮平疗效的相关性。结果 2组家庭年收入、家庭关系、卒中次数、病灶数目、NIHSS评分、ADL评分比较差异均有统计学意义（均P＜0.05）。基因多态性检测结果显示，抑郁组LL型28例（36.8%）、SL型26例（34.2%）、SS型22例（28.9%），非抑郁组LL型16例（16.7%）、SL型42例（43.8%）、SS型38例（39.6%），2组基因型分布比较差异有统计学意义（P=0.033）。多因素Logistic回归分析结果显示，卒中次数、病灶数目、NIHSS评分、ADL评分是急性脑卒中后抑郁的独立影响因素（均P＜0.05）；将上述因素与MAOA-uVNTR基因代入Logistic回归模型进行交互作用分析，结果显示NIHSS评分与MAOA-uVNTR基因存在交互作用（P＜0.05）。奥氮平治疗后，LL型、SL型、SS型患者HAMD、NIHSS评分均低于治疗前，ADL评分高于治疗前，且SL型和SS型患者HAMD、NIHSS评分均低于LL型患者，ADL评分高于LL型患者（均P＜0.05）；以LL型为参考，奥氮平对SS型的疗效更优（比值比=2.786，95%置信区间：2.432~3.564，P=0.016）。结论 MAOA基因多态性与急性脑卒中后抑郁及奥氮平疗效存在相关性。

• Objective To investigate the relationship of monoamine oxidase A (MAOA) gene polymorphism with depression after acute stroke and therapeutic effect of olanzapine. Methods  From September 2020 to September 2022, 172 patients with acute stroke admitted to Zhujiang Hospital of Southern Medical University were enrolled retrospectively. According to the Hamilton Depression Scale (HAMD) score, patients were divided into depression group (HAMD score≥8, 76 cases) and non depression group (HAMD score <8, 96 cases), and patients in the depression group were given olanzapine orally. Genotype and allele distribution of MAOA-variable number of tandem repeat(MAOA-uVNTR) in all patients were detected, and general data, HAMD score, National Institute of Health Stroke Scale (NIHSS) score and activity of daily living scale (ADL) score in all patients before treatment and the scores in the depression group after treatment were collected. Multivariate Logistic regression analysis was used to analyze influencing factors of depression after acute stroke, interaction between MAOA gene polymorphism and influencing factors, and relationship of different genotypes with therapeutic effect of olanzapine. Results There were statistically significant differences between the two groups in annual household income, family relationship, stroke frequency, the number of lesions, NIHSS score and ADL score (all P<0.05). The gene polymorphism detection showed that there were 28 cases (36.8%) of LL genotype, 26 cases (34.2%) of SL genotype and 22 cases (28.9%) of SS genotype in the depression group, and 16 cases (16.7%) of LL genotype, 42 cases (43.8%) of SL genotype and 38 cases (39.6%) of SS genotype in the non depression group. The difference in genotype distribution between the two groups was statistically significant(P=0.033). Multivariate Logistic regression analysis showed that stroke frequency, the number of lesions, NIHSS score and ADL score were independent influencing factors of depression after acute stroke (all P<0.05). The above factors and MAOA-uVNTR gene were put into Logistic regression model for interaction analysis, and it was shown that NIHSS score had interaction with MAOA-uVNTR gene(P<0.05). The scores of HAMD and NIHSS in patients with LL, SL and SS genotypes treatment by olanzapine were lower than those before treatment, and the score of ADL was higher than that before treatment; the scores of HAMD and NIHSS in patients with SL and SS genotypes were lower than those in patients with LL genotype, and the score of ADL was higher than that in patients with LL genotype (all P<0.05). With the LL genotype as a reference, therapeutic effect of olanzapine was superior in treating patients with SS genotype (odds ratio=2.786, 95% confidence interval: 2.432-3.564, P=0.016). Conclusion MAOA gene polymorphism is associated with depression after acute stroke and the therapeutic effect of olanzapine.