Dataset Information

Can Lipid-Lowering Drugs Reduce the Risk of Cholelithiasis? A Mendelian Randomization Study.

ABSTRACT:

Background and aims

Cholelithiasis etiology intricately involves lipid metabolism. We sought to investigate the plausible causal link between genetically proxied lipid-lowering medications-specifically HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors-and cholelithiasis risk.

Methods

Our study utilized two genetic instruments for exposure to lipid-lowering drugs. These instruments encompassed genetic variants linked to low-density lipoprotein (LDL) cholesterol within or in proximity to drug target genes, along with loci governing gene expression traits of these targets. Effect estimates were derived through Inverse-variance-weighted MR (IVW-MR) and summary-data-based MR (SMR) methods.

Results

Higher HMGCR-mediated LDL cholesterol levels (IVW-MR, OR = 2.15, 95% CI = 1.58-2.94; P = 0.000) and increased HMGCR expression (SMR, OR = 1.19, 95% CI = 1.04-1.37; P = 0.014) are linked to elevated cholelithiasis risk, suggesting potential benefits of HMGCR inhibition. In contrast, higher PCSK9-mediated LDL cholesterol levels (IVW-MR, OR = 0.72, 95% CI = 0.56-0.94; P = 0.015) and increased PCSK9 expression (SMR, OR = 0.90, 95% CI = 0.82-0.99; P = 0.035) both correlate with lower cholelithiasis risk, indicating that PCSK9 inhibition may elevate this risk. Nevertheless, no substantial link emerged between NPC1L1-mediated LDL cholesterol or NPC1L1 expression and cholelithiasis in both IVW-MR and SMR analyses.

Conclusion

This MR investigation affirms the causal link between the utilization of HMGCR inhibitors and a diminished risk of cholelithiasis. Additionally, it indicates a causal link between PCSK9 inhibitors use and increased cholelithiasis risk. However, no significant correlation was found between NPC1L1 inhibitors use and cholelithiasis risk.

SUBMITTER: Dong H

PROVIDER: S-EPMC10896097 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

Can Lipid-Lowering Drugs Reduce the Risk of Cholelithiasis? A Mendelian Randomization Study.

Dong Hao H Chen Rong R Xu Fang F Cheng Fang F

Clinical epidemiology 20240222

<h4>Background and aims</h4>Cholelithiasis etiology intricately involves lipid metabolism. We sought to investigate the plausible causal link between genetically proxied lipid-lowering medications-specifically HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors-and cholelithiasis risk.<h4>Methods</h4>Our study utilized two genetic instruments for exposure to lipid-lowering drugs. These instruments encompassed genetic variants linked to low-density lipoprotein (LDL) cholesterol within or in ...[more]

PMID: 38410417

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Dataset Information

Can Lipid-Lowering Drugs Reduce the Risk of Cholelithiasis? A Mendelian Randomization Study.

Background and aims

Methods

Results

Conclusion

Publications

Can Lipid-Lowering Drugs Reduce the Risk of Cholelithiasis? A Mendelian Randomization Study.

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