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Genetic variations in HMGCR and PCSK9 and kidney function: a Mendelian randomization study
DC Field | Value | Language |
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dc.contributor.author | Park, Sehoon | - |
dc.contributor.author | Kim, Seong Geun | - |
dc.contributor.author | Lee, Soojin | - |
dc.contributor.author | Kim, Yaerim | - |
dc.contributor.author | Cho, Semin | - |
dc.contributor.author | Kim, Kwangsoo | - |
dc.contributor.author | Kim, Yong Chul | - |
dc.contributor.author | Han, Seung Seok | - |
dc.contributor.author | Lee, Hajeong | - |
dc.contributor.author | Lee, Jung Pyo | - |
dc.contributor.author | Joo, Kwon Wook | - |
dc.contributor.author | Lim, Chun Soo | - |
dc.contributor.author | Kim, Yon Su | - |
dc.contributor.author | Kim, Dong Ki | - |
dc.date.accessioned | 2024-08-08T01:20:41Z | - |
dc.date.available | 2024-08-08T01:20:41Z | - |
dc.date.created | 2023-08-31 | - |
dc.date.created | 2023-08-31 | - |
dc.date.issued | 2023-07 | - |
dc.identifier.citation | Kidney Research and Clinical Practice, Vol.42 No.4, pp.460-472 | - |
dc.identifier.issn | 2211-9132 | - |
dc.identifier.uri | https://hdl.handle.net/10371/205233 | - |
dc.description.abstract | Background: The genetically predicted lipid-lowering effect of HMGCR or PCSK9 variant can be used to assess drug proxy effects on kidney function. Methods: Mendelian randomization (MR) analysis-identified HMGCR and PCSK9 genetic variants were used to predict the low-densi-ty lipoprotein (LDL) cholesterol-lowering effects of medications targeting related molecules. Primary summary-level outcome data for log-estimated glomerular filtration rate (eGFR; creatinine) were provided by the CKDGen Consortium (n = 1,004,040 European) from a meta-analysis of CKDGen and UK Biobank data. We also conducted a separate investigation of summary-level data from CKDGen (n = 567,460, log-eGFR [creatinine]) and UK Biobank (n = 436,581, log-eGFR [cystatin C]) samples. Summary-level MRs using an in-verse variance weighted method and pleiotropy-robust methods were performed. Results: Summary-level MR analysis indicated that the LDL-lowering effect predicted genetically by HMGCR variants (50-mg/dL de-crease) was significantly associated with a decrease in eGFR (–1.67%; 95% confidence interval [CI], –2.20% to – 1.13%). Similar significance was found in results from the pleiotropy-robust MR methods when the CKDGen and UK Biobank data were analyzed sepa-rately. However, the LDL-lowering effect predicted genetically by PCSK9 variants was significantly associated with an increase in eGFR (+1.17%; 95% CI, 0.10%–2.25%). The results were similarly supported by the weighted median method and in each CKDGen and UK Biobank dataset, but the significance obtained by MR-Egger regression was attenuated. Conclusion: Genetically predicted HMG-CoA reductase inhibition was associated with low eGFR, while genetically predicted PCSK9 inhibition was associated with high eGFR. Clinicians should consider that the direct effect of different types of lipid-lowering medica-tion on kidney function can vary. | - |
dc.language | 영어 | - |
dc.publisher | 대한신장학회 | - |
dc.title | Genetic variations in HMGCR and PCSK9 and kidney function: a Mendelian randomization study | - |
dc.type | Article | - |
dc.identifier.doi | 10.23876/j.krcp.22.237 | - |
dc.citation.journaltitle | Kidney Research and Clinical Practice | - |
dc.identifier.wosid | 001124236700006 | - |
dc.identifier.scopusid | 2-s2.0-85166407504 | - |
dc.citation.endpage | 472 | - |
dc.citation.number | 4 | - |
dc.citation.startpage | 460 | - |
dc.citation.volume | 42 | - |
dc.identifier.kciid | ART003004662 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Kim, Yong Chul | - |
dc.contributor.affiliatedAuthor | Lee, Jung Pyo | - |
dc.contributor.affiliatedAuthor | Joo, Kwon Wook | - |
dc.contributor.affiliatedAuthor | Lim, Chun Soo | - |
dc.contributor.affiliatedAuthor | Kim, Yon Su | - |
dc.contributor.affiliatedAuthor | Kim, Dong Ki | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordAuthor | Chronic kidney disease | - |
dc.subject.keywordAuthor | Dyslipidaemia | - |
dc.subject.keywordAuthor | Mendelian randomization | - |
dc.subject.keywordAuthor | Statin | - |
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