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. 2024 Oct 25;103(43):e40194.
doi: 10.1097/MD.0000000000040194.

Assessing the effects of HMGCR, LPL, and PCSK9 inhibition on sleep apnea: Mendelian randomization analysis of drug targets

Wei Tan  1 , Xiujuan Deng  2 , Xiaoning Tan  3 , Guangbo Tan  2
Affiliations

Assessing the effects of HMGCR, LPL, and PCSK9 inhibition on sleep apnea: Mendelian randomization analysis of drug targets

Wei Tan et al. Medicine (Baltimore). .

Abstract

To investigate the use of lipid-lowering drugs and abnormal serum lipid levels in patients at risk of sleep apnea syndrome. Three types of Mendelian randomization (MR) analyses were used. First, a 2-sample Mendelian randomization (TSMR) analysis was used to investigate the association between sleep apnea syndrome risk and serum lipid levels. Multivariate Mendelian randomization (MVMR) analysis was subsequently used to investigate the effects of confounding variables on SAS incidence of sleep apnea syndrome. Finally, drug-target Mendelian randomization (DMR) analysis was used to analyze the association between lipid-lowering drug use and sleep apnea syndrome risk. According to the TSMR analysis, the serum HDL-C concentration was negatively correlated with sleep apnea syndrome (OR = 0.904; 95% CI = 0.845-0.967; P = .003). Serum TG levels were positively correlated with sleep apnea syndrome (OR = 1.081; 95% CI = 1.003-1.163; P = .039). The association between serum HDL-C levels and sleep apnea syndrome in patients with MVMR was consistent with the results in patients with TSMR (OR = 0.731; 95% CI = 0.500-1.071; P = 3.94E-05). According to our DMR analysis, HMGCR and PCSK9, which act by lowering serum LDL-C levels, were inversely associated with the risk of sleep apnea syndrome (OR = 0.627; 95% CI = 0.511-0.767; P = 6.30E-06) (OR = 0.775; 95% CI = 0.677-0.888; P = .0002). LPL, that lowered serum TG levels, was positively associated with the risk of sleep apnea syndrome (OR = 1.193; 95% CI = 1.101-1.294; P = 1.77E-05). Our analysis suggested that high serum HDL-C levels may reduce the risk of sleep apnea syndrome. Low serum TG levels have a protective effect against sleep apnea syndrome. The DMR results suggested that the use of HMGCR lipid-lowering drugs (such as statins) and PCSK9 inhibitors has a protective effect against sleep apnea syndrome. However, LPL-based lipid-lowering drugs may increase the risk of sleep apnea syndrome.

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Figures

Figure 1.
Figure 1.
Design scheme of this study.
Figure 2.
Figure 2.
The results of the TSMR analysis of the associations between LDL-C, HDL-C, TG, and TC and sleep apnea syndrome risk were obtained using the IVW, MR-Egger, and weighted median methods. The lipid levels mentioned above were validated using CHD as a positive control. number of SNPs.
Figure 3.
Figure 3.
Results of MVMR analysis.
Figure 4.
Figure 4.
DMR analysis of the 8 drug targets. DMR validation analysis of the above drug targets and CHD incidence. Number of SNPs.
See this image and copyright information in PMC

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