Fan Lin, You Yiwen, Fan Yao, Shen Chong, Xue Yong
Department of Pharmacy, Huai'an Third People's Hospital, Huai'an, People's Republic of China.
Division of Clinical Epidemiology, Affiliated Geriatric Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
Neuropsychiatr Dis Treat. 2021 Apr 30;17:1289-1297. doi: 10.2147/NDT.S305200. eCollection 2021.
Dyslipidemia frequently occurs in schizophrenia patients treated with antipsychotic drugs (APDs), especially atypical APDs. Apolipoprotein A1 (ApoA1) plays a key role in lipid metabolism. The aim of this study was to investigate whether ApoA1 gene polymorphisms are associated with APD-induced dyslipidemia in schizophrenia patients.
A total of 1987 patients with schizophrenia were enrolled in this study. Serum lipid profiles were determined with a biochemistry analyzer. Genotyping for the rs5072 polymorphism of ApoA1 was performed with TaqMan assay. Logistic regression analysis was carried out to evaluate the relationship between ApoA1 gene polymorphisms and APD-induced dyslipidemia. The effects of drug classification (typical vs atypical APD) and drug regimen (monotherapy vs combination therapy) on serum lipid levels were also analyzed.
A significant association was found between rs5072 and triglyceride (TG) levels in the recessive model of the logistic regression analysis (adjusted odds ratio [OR]=1.50, 95% confidence interval [CI]: 1.03, 2.17; P<0.05). TG level was significantly higher in patients treated with combination therapy (1.03 (0.71, 1.51) mmol/l) compared to monotherapy (0.93 (0.67, 1.43) mmol/l) and was also associated with sex. There were significant differences in TG levels among the three genotypes of ApoA1 rs5072 (GG, GA, and AA) in the whole study population and in patients treated with atypical APDs.
The ApoA1 rs5072 variant is associated with dysregulated TG metabolism in schizophrenia patients treated with APDs, which may increase susceptibility to dyslipidemia.
血脂异常在接受抗精神病药物(APDs)治疗的精神分裂症患者中经常出现,尤其是非典型抗精神病药物。载脂蛋白A1(ApoA1)在脂质代谢中起关键作用。本研究的目的是调查ApoA1基因多态性是否与精神分裂症患者中APD诱导的血脂异常相关。
本研究共纳入1987例精神分裂症患者。用生化分析仪测定血脂谱。采用TaqMan分析法对ApoA1的rs5072多态性进行基因分型。进行逻辑回归分析以评估ApoA1基因多态性与APD诱导的血脂异常之间的关系。还分析了药物分类(典型与非典型APD)和药物治疗方案(单药治疗与联合治疗)对血脂水平的影响。
在逻辑回归分析的隐性模型中,发现rs5072与甘油三酯(TG)水平之间存在显著关联(调整后的优势比[OR]=1.50,95%置信区间[CI]:1.03,2.17;P<0.05)。与单药治疗(0.93(0.67,1.43)mmol/l)相比,联合治疗患者的TG水平(1.03(0.71,1.51)mmol/l)显著更高,且与性别也相关。在整个研究人群和接受非典型APD治疗的患者中,ApoA1 rs5072的三种基因型(GG、GA和AA)之间的TG水平存在显著差异。
ApoA1 rs5072变异与接受APD治疗的精神分裂症患者的TG代谢失调相关,这可能增加血脂异常的易感性。