Lipid-lowering drugs and inflammatory bowel disease’s risk: a drug-target Mendelian randomization study
Abstract Background Inflammatory bowel disease (IBD) has been associated with lipid-lowering drugs in observational studies. Drug-target Mendelian randomization (MR) was utilized in this study to examine the causal relationship between lipid-lowering drugs and incidence of IBD, aiming to identify ne...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Diabetology & Metabolic Syndrome |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13098-023-01252-1 |
| _version_ | 1797355681060225024 |
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| author | Jiaxi Zhao Rong Chen Mengqi Luo Hongping Gong Kaixin Li Qian Zhao |
| author_facet | Jiaxi Zhao Rong Chen Mengqi Luo Hongping Gong Kaixin Li Qian Zhao |
| author_sort | Jiaxi Zhao |
| collection | DOAJ |
| description | Abstract Background Inflammatory bowel disease (IBD) has been associated with lipid-lowering drugs in observational studies. Drug-target Mendelian randomization (MR) was utilized in this study to examine the causal relationship between lipid-lowering drugs and incidence of IBD, aiming to identify new preventive uses for the drugs. Methods We identified instrumental variables for three classes of lipid-lowering drugs: HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors, using data from the Global Lipids Genetics Consortium. Summary statistics of IBD were obtained from UK Inflammatory Bowel Disease Genetics. The summary-data-based MR (SMR) and the inverse-variance weighted (IVW) MR were used for analysis. Sensitivity analyses were performed by conventional MR methods. Results The SMR analysis showed no significant genetic association between increased gene expression of HMGCR, PCSK9, and NPC1L1 and IBD, Crohn’s disease (CD) and ulcerative colitis (UC). According to IVW-MR analysis, increased HMGCR expression is associated with a reduced risk of IBD (OR = 0.73, 95% confidence interval (CI) 0.59–0.90, P = 0.003) and CD (OR = 0.75, 95% CI 0.57–0.97, P = 0.03), but not with UC. Additionally, increased NPC1L1 gene expression was associated with elevated risk of IBD (OR = 1.60, 95% CI 1.07–2.40, P = 0.023), but not with CD and UC. However, no significant causal relationships were found between PCSK9 gene expression and IBD, CD, and UC. The sensitivity analysis demonstrated no evidence of heterogeneity or pleiotropy among the reported results. Conclusions The heightened expression of genetic variations in HMGCR inhibitor targets could potentially reduce the risk of IBD and CD, while genetic variation in the expression of NPC1L1 targets was positively associated with IBD. |
| first_indexed | 2024-03-08T14:14:36Z |
| format | Article |
| id | doaj.art-e24584de02384d41952f5c24f6ca72ea |
| institution | Directory Open Access Journal |
| issn | 1758-5996 |
| language | English |
| last_indexed | 2024-03-08T14:14:36Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Diabetology & Metabolic Syndrome |
| spelling | doaj.art-e24584de02384d41952f5c24f6ca72ea2024-01-14T12:30:52ZengBMCDiabetology & Metabolic Syndrome1758-59962024-01-011611810.1186/s13098-023-01252-1Lipid-lowering drugs and inflammatory bowel disease’s risk: a drug-target Mendelian randomization studyJiaxi Zhao0Rong Chen1Mengqi Luo2Hongping Gong3Kaixin Li4Qian Zhao5General Practice Ward/International Medical Center Ward General Practice Medical Center, West China Hospital, Sichuan UniversityDepartment of Rehabilitation Medicine, The First Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Gastroenterology and Hepatology, West China Hospital, Sichuan UniversityGeneral Practice Ward/International Medical Center Ward General Practice Medical Center, West China Hospital, Sichuan UniversityDepartment of Nephrology, Huadong HospitalGeneral Practice Ward/International Medical Center Ward General Practice Medical Center, West China Hospital, Sichuan UniversityAbstract Background Inflammatory bowel disease (IBD) has been associated with lipid-lowering drugs in observational studies. Drug-target Mendelian randomization (MR) was utilized in this study to examine the causal relationship between lipid-lowering drugs and incidence of IBD, aiming to identify new preventive uses for the drugs. Methods We identified instrumental variables for three classes of lipid-lowering drugs: HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitors, using data from the Global Lipids Genetics Consortium. Summary statistics of IBD were obtained from UK Inflammatory Bowel Disease Genetics. The summary-data-based MR (SMR) and the inverse-variance weighted (IVW) MR were used for analysis. Sensitivity analyses were performed by conventional MR methods. Results The SMR analysis showed no significant genetic association between increased gene expression of HMGCR, PCSK9, and NPC1L1 and IBD, Crohn’s disease (CD) and ulcerative colitis (UC). According to IVW-MR analysis, increased HMGCR expression is associated with a reduced risk of IBD (OR = 0.73, 95% confidence interval (CI) 0.59–0.90, P = 0.003) and CD (OR = 0.75, 95% CI 0.57–0.97, P = 0.03), but not with UC. Additionally, increased NPC1L1 gene expression was associated with elevated risk of IBD (OR = 1.60, 95% CI 1.07–2.40, P = 0.023), but not with CD and UC. However, no significant causal relationships were found between PCSK9 gene expression and IBD, CD, and UC. The sensitivity analysis demonstrated no evidence of heterogeneity or pleiotropy among the reported results. Conclusions The heightened expression of genetic variations in HMGCR inhibitor targets could potentially reduce the risk of IBD and CD, while genetic variation in the expression of NPC1L1 targets was positively associated with IBD.https://doi.org/10.1186/s13098-023-01252-1Inflammatory bowel diseaseLipid- lowering drugMendelian randomizationCrohn’s diseaseUlcerative colitis |
| spellingShingle | Jiaxi Zhao Rong Chen Mengqi Luo Hongping Gong Kaixin Li Qian Zhao Lipid-lowering drugs and inflammatory bowel disease’s risk: a drug-target Mendelian randomization study Diabetology & Metabolic Syndrome Inflammatory bowel disease Lipid- lowering drug Mendelian randomization Crohn’s disease Ulcerative colitis |
| title | Lipid-lowering drugs and inflammatory bowel disease’s risk: a drug-target Mendelian randomization study |
| title_full | Lipid-lowering drugs and inflammatory bowel disease’s risk: a drug-target Mendelian randomization study |
| title_fullStr | Lipid-lowering drugs and inflammatory bowel disease’s risk: a drug-target Mendelian randomization study |
| title_full_unstemmed | Lipid-lowering drugs and inflammatory bowel disease’s risk: a drug-target Mendelian randomization study |
| title_short | Lipid-lowering drugs and inflammatory bowel disease’s risk: a drug-target Mendelian randomization study |
| title_sort | lipid lowering drugs and inflammatory bowel disease s risk a drug target mendelian randomization study |
| topic | Inflammatory bowel disease Lipid- lowering drug Mendelian randomization Crohn’s disease Ulcerative colitis |
| url | https://doi.org/10.1186/s13098-023-01252-1 |
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