Can Lipid-Lowering Drugs Reduce the Risk of Cholelithiasis? A Mendelian Randomization Study
Hao Dong,1,* Rong Chen,2,* Fang Xu,3,* Fang Cheng4 1Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Rehabilitation Medicine, the First Affiliated Hospital of S...
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Dove Medical Press
2024-02-01
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| Series: | Clinical Epidemiology |
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| Online Access: | https://www.dovepress.com/can-lipid-lowering-drugs-reduce-the-risk-of-cholelithiasis-a-mendelian-peer-reviewed-fulltext-article-CLEP |
| _version_ | 1797299907579609088 |
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| author | Dong H Chen R Xu F Cheng F |
| author_facet | Dong H Chen R Xu F Cheng F |
| author_sort | Dong H |
| collection | DOAJ |
| description | Hao Dong,1,* Rong Chen,2,* Fang Xu,3,* Fang Cheng4 1Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Rehabilitation Medicine, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 3Clinical Medical Laboratory Center, Taizhou People’s Hospital, Taizhou, Jiangsu, 225300, People’s Republic of China; 4Department of Gastroenterology, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fang Cheng, Department of Gastroenterology, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, No. 1 Yintan Road, Dongxihu District, Wuhan, 430023, Hubei Province, People’s Republic of China, Email 13886178189@163.comBackground 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.Keywords: cholelithiasis, lipid-lowering drugs, Mendelian randomization analysis, HMGCR inhibitors, PCSK9 inhibitors, NPC1L1 inhibitors |
| first_indexed | 2024-03-07T22:58:29Z |
| format | Article |
| id | doaj.art-a7a41f59e6f64ba48716ce88ae69207a |
| institution | Directory Open Access Journal |
| issn | 1179-1349 |
| language | English |
| last_indexed | 2024-03-07T22:58:29Z |
| publishDate | 2024-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Clinical Epidemiology |
| spelling | doaj.art-a7a41f59e6f64ba48716ce88ae69207a2024-02-22T18:28:24ZengDove Medical PressClinical Epidemiology1179-13492024-02-01Volume 1613114190654Can Lipid-Lowering Drugs Reduce the Risk of Cholelithiasis? A Mendelian Randomization StudyDong HChen RXu FCheng FHao Dong,1,* Rong Chen,2,* Fang Xu,3,* Fang Cheng4 1Department of Gastroenterology and Hepatology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Rehabilitation Medicine, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 3Clinical Medical Laboratory Center, Taizhou People’s Hospital, Taizhou, Jiangsu, 225300, People’s Republic of China; 4Department of Gastroenterology, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fang Cheng, Department of Gastroenterology, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, No. 1 Yintan Road, Dongxihu District, Wuhan, 430023, Hubei Province, People’s Republic of China, Email 13886178189@163.comBackground 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.Keywords: cholelithiasis, lipid-lowering drugs, Mendelian randomization analysis, HMGCR inhibitors, PCSK9 inhibitors, NPC1L1 inhibitorshttps://www.dovepress.com/can-lipid-lowering-drugs-reduce-the-risk-of-cholelithiasis-a-mendelian-peer-reviewed-fulltext-article-CLEPcholelithiasislipid-lowering drugsmendelian randomization analysishmgcr inhibitorspcsk9 inhibitorsnpc1l1 inhibitors. |
| spellingShingle | Dong H Chen R Xu F Cheng F Can Lipid-Lowering Drugs Reduce the Risk of Cholelithiasis? A Mendelian Randomization Study Clinical Epidemiology cholelithiasis lipid-lowering drugs mendelian randomization analysis hmgcr inhibitors pcsk9 inhibitors npc1l1 inhibitors. |
| title | Can Lipid-Lowering Drugs Reduce the Risk of Cholelithiasis? A Mendelian Randomization Study |
| title_full | Can Lipid-Lowering Drugs Reduce the Risk of Cholelithiasis? A Mendelian Randomization Study |
| title_fullStr | Can Lipid-Lowering Drugs Reduce the Risk of Cholelithiasis? A Mendelian Randomization Study |
| title_full_unstemmed | Can Lipid-Lowering Drugs Reduce the Risk of Cholelithiasis? A Mendelian Randomization Study |
| title_short | Can Lipid-Lowering Drugs Reduce the Risk of Cholelithiasis? A Mendelian Randomization Study |
| title_sort | can lipid lowering drugs reduce the risk of cholelithiasis a mendelian randomization study |
| topic | cholelithiasis lipid-lowering drugs mendelian randomization analysis hmgcr inhibitors pcsk9 inhibitors npc1l1 inhibitors. |
| url | https://www.dovepress.com/can-lipid-lowering-drugs-reduce-the-risk-of-cholelithiasis-a-mendelian-peer-reviewed-fulltext-article-CLEP |
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