Association Between ApoA1 Gene Polymorphisms and Antipsychotic Drug-Induced Dyslipidemia in Schizophrenia

Neuropsychiatr Dis Treat. 2021 Apr 30:17:1289-1297. doi: 10.2147/NDT.S305200. eCollection 2021.

Abstract

Purpose: 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.

Patients and methods: 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.

Results: 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.

Conclusion: The ApoA1 rs5072 variant is associated with dysregulated TG metabolism in schizophrenia patients treated with APDs, which may increase susceptibility to dyslipidemia.

Keywords: antipsychotic drug; apolipoprotein A1; dyslipidemia; gene polymorphism; schizophrenia.