Association of lipid-modifying therapy with risk of obstructive sleep apnea: A drug-target mendelian randomization study.
Toxicol Appl Pharmacol
; 485: 116909, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38521370
ABSTRACT
BACKGROUND:
Obstructive sleep apnea (OSA) is considered to be an important contributor of dyslipidemia. However, there lacks observational studies focusing on the potential effect of lipid management on OSA risk. Thus, we aimed to investigate the genetic association of lipid-modifying therapy with risk of OSA.METHODS:
A drug-target mendelian randomization (MR) study using both cis-variants and cis-expression quantitative trait loci (eQTLs) of lipid-modifying drug targets was performed. The MR analyses used summary-level data of genome wide association studies (GWAS). Primary MR analysis was conducted using inverse-variance-weighted (IVW) method. Sensitivity analysis was performed using weighted median (WM) and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods.RESULTS:
Genetically proxied low-density lipoprotein cholesterol (LDL-C)-lowering effect of cholesteryl ester transfer protein (CETP) was associated with reduced risk of OSA (odds ratio [OR] =0.75, 95% confidence interval [CI] 0.60-0.94, false discovery rate [FDR] q value = 0.046). A significant MR association with risk of OSA was observed for CETP expression in subcutaneous adipose tissue (OR = 0.94, 95%CI 0.89-1.00, FDR q value = 0.049), lung (OR = 0.94, 95%CI 0.89-1.00, FDR q value = 0.049) and small intestine (OR = 0.96, 95%CI 0.93-1.00, FDR q value = 0.049). No significant effects of high-density lipoprotein cholesterol (HDL-C)-raising effect of CETP inhibition, LDL-C-lowering and triglycerides-lowering effect of other drug targets on OSA risk were observed.CONCLUSIONS:
The present study presented genetic evidence supporting the association of LDL-C-lowering therapy by CETP inhibition with reduced risk of OSA. These findings provided novel insights into the role of lipid management in patients with OSA and encouraged further clinical validations and mechanistic investigations.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apneia Obstrutiva do Sono
/
Proteínas de Transferência de Ésteres de Colesterol
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Estudo de Associação Genômica Ampla
/
Análise da Randomização Mendeliana
Limite:
Humans
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China