| Title: | Novel insights into causal effects of serum lipids and lipid-modifying targets on cholelithiasis |
| Journal: | Gut |
| Published: | 9 Nov 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37945330/ |
| DOI: | https://doi.org/10.1136/gutjnl-2023-330784 |
Publication 8364
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
OBJECTIVE: Different serum lipids and lipid-modifying targets should affect the risk of cholelithiasis differently, however, whether such effects are causal is still controversial and we aimed to answer this question.</p>
DESIGN: We prospectively estimated the associations of four serum lipids with cholelithiasis in UK Biobank using the Cox proportional hazard model, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Furthermore, we estimated the causal associations of the genetically predicted serum lipids with cholelithiasis in Europeans using the Mendelian randomisation (MR) design. Finally, both drug-target MR and colocalisation analyses were performed to estimate the lipid-modifying targets' effects on cholelithiasis, including HMGCR, NPC1L1, PCSK9, APOB, LDLR, ACLY, ANGPTL3, MTTP, PPARA, PPARD and PPARG.</p>
RESULTS: We found that serum levels of LDL-C and HDL-C were inversely associated with cholelithiasis risk and such associations were linear. However, the serum level of TC was non-linearly associated with cholelithiasis risk where lower TC was associated with higher risk of cholelithiasis, and the serum TG should be in an inverted 'U-shaped' relationship with it. The MR analyses supported that lower TC and higher TG levels were two independent causal risk factors. The drug-target MR analysis suggested that HMGCR inhibition should reduce the risk of cholelithiasis, which was corroborated by colocalisation analysis.</p>
CONCLUSION: Lower serum TC can causally increase the risk of cholelithiasis. The cholelithiasis risk would increase with the elevation of serum TG but would decrease when exceeding 2.57 mmol/L. The use of HMGCR inhibitors should prevent its risk.</p>
8 Authors
- Lanlan Chen
- Wei Qiu
- Xiaodong Sun
- Menghan Gao
- Yuexuan Zhao
- Mingyue Li
- Zhongqi Fan
- Guoyue Lv
Enabling scientific discoveries that improve human health