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Genetic association of lipids and lipid lowering drug target genes with sarcoidosis.
- Source :
-
Scientific reports [Sci Rep] 2024 Oct 17; Vol. 14 (1), pp. 24351. Date of Electronic Publication: 2024 Oct 17. - Publication Year :
- 2024
-
Abstract
- To determine the potential causal association between serum lipid levels and sarcoidosis, and to investigate the potential impact of lipid lowering agents on sarcoidosis. Two-sample Mendelian randomization (TSMR) was used to investigate the association between lipid levels (including LDL-c, HDL-c, TG, and TC) and sarcoidosis risk. In addition, we used Mendelian drug target randomization (DMR) to analyze the relationship between drug targets for lowering LDL-c levels (HMGCR, PCSK9, and NPC1L1) and drug targets for lowering TG levels (LPL and APOC3) and the risk of sarcoidosis. According to the TSMR analysis, a positive correlation was observed between the serum LDL-c concentration and sarcoidosis incidence (n = 153 SNPs, OR = 1.232, 95% CI = 1.018-1.491; p = 0.031). Similarly, serum TG concentration was found to be positively associated with sarcoidosis (n = 52 SNPs, OR = 1.287, 95% CI = 1.024-1.617; p = 0.03). The DMR results demonstrated a positive correlation between PCSK9-mediated serum LDL-c levels and sarcoidosis (n = 35 SNPs, OR = 1.681, 95% CI = 1.220-2.315; p = 0.001). Similarly, serum TG levels mediated by LPL were positively associated with sarcoidosis (n = 28 SNPs, OR = 1.569, 95% CI = 1.223-2.012; p = 0.0003). This study suggested that elevated serum TG and LDL-c levels may increase the risk of sarcoidosis. PCSK9-mediated reduction of LDL-C levels (simulating the effects of PCSK9 inhibitors) and LPL-mediated reduction of TG levels (simulating the effects of LPL-related lipid lowering drugs) can decrease the risk of developing sarcoidosis.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Hypolipidemic Agents therapeutic use
Triglycerides blood
Lipids blood
Lipoprotein Lipase genetics
Genetic Predisposition to Disease
Membrane Transport Proteins genetics
Cholesterol, HDL blood
Hydroxymethylglutaryl CoA Reductases
Sarcoidosis genetics
Sarcoidosis drug therapy
Sarcoidosis blood
Polymorphism, Single Nucleotide
Mendelian Randomization Analysis
Cholesterol, LDL blood
Proprotein Convertase 9 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 39420052
- Full Text :
- https://doi.org/10.1038/s41598-024-75322-3