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Genetic evidence implicating circulating lipids and lipid drug targets in pterygium
There is limited knowledge about the impact of circulating lipids and lipid-modifying drugs on pterygium development, with conflicting results reported. Our study aimed to address these questions by applying the Mendelian randomization (MR) approach. A two-step MR model was developed. In the first s...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Research Network of Computational and Structural Biotechnology
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663701/ https://www.ncbi.nlm.nih.gov/pubmed/38022695 http://dx.doi.org/10.1016/j.csbj.2023.11.002 |
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author | Cai, Yuchen Fang, Fei Zhou, Tianyi Shi, Wenjun Cai, Xueyao Fu, Yao |
author_facet | Cai, Yuchen Fang, Fei Zhou, Tianyi Shi, Wenjun Cai, Xueyao Fu, Yao |
author_sort | Cai, Yuchen |
collection | PubMed |
description | There is limited knowledge about the impact of circulating lipids and lipid-modifying drugs on pterygium development, with conflicting results reported. Our study aimed to address these questions by applying the Mendelian randomization (MR) approach. A two-step MR model was developed. In the first step, bidirectional two-sample MR was employed to establish the causal relationship between circulating lipids and pterygium risk. In the second step, drug-target MR analysis was conducted to assess the causal effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitors on pterygium outcomes. Genetically predicted low-density lipoprotein cholesterol (LDL-c) levels were found to be significantly associated with an increased risk of pterygium (Inverse variance weighted [IVW] odds ratio [OR] = 2.227; P = 1.53 × 10(–4)). Similarly, higher total cholesterol (TC) levels exhibited a suggestive association with greater susceptibility to pterygium (IVW OR = 1.806; P = 1.70 × 10(–3)). Through drug-target MR, a positive causal association was noted between HMGCR-mediated LDL-c levels and pterygium (IVW OR = 6.999; P = 0.016), suggesting that statins may be effective in reducing pterygium risk. The present findings suggest that circulating TC and LDL-c are risk factors for pterygium. Additionally, the results indicate that HMGCR inhibitors, which lower LDL-c levels, have a potential protective effect on pterygium outcomes. Further research is warranted to elucidate the underlying mechanisms involved in pterygium pathogenesis, with a particular focus on cholesterol metabolism. |
format | Online Article Text |
id | pubmed-10663701 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Research Network of Computational and Structural Biotechnology |
record_format | MEDLINE/PubMed |
spelling | pubmed-106637012023-11-04 Genetic evidence implicating circulating lipids and lipid drug targets in pterygium Cai, Yuchen Fang, Fei Zhou, Tianyi Shi, Wenjun Cai, Xueyao Fu, Yao Comput Struct Biotechnol J Research Article There is limited knowledge about the impact of circulating lipids and lipid-modifying drugs on pterygium development, with conflicting results reported. Our study aimed to address these questions by applying the Mendelian randomization (MR) approach. A two-step MR model was developed. In the first step, bidirectional two-sample MR was employed to establish the causal relationship between circulating lipids and pterygium risk. In the second step, drug-target MR analysis was conducted to assess the causal effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitors on pterygium outcomes. Genetically predicted low-density lipoprotein cholesterol (LDL-c) levels were found to be significantly associated with an increased risk of pterygium (Inverse variance weighted [IVW] odds ratio [OR] = 2.227; P = 1.53 × 10(–4)). Similarly, higher total cholesterol (TC) levels exhibited a suggestive association with greater susceptibility to pterygium (IVW OR = 1.806; P = 1.70 × 10(–3)). Through drug-target MR, a positive causal association was noted between HMGCR-mediated LDL-c levels and pterygium (IVW OR = 6.999; P = 0.016), suggesting that statins may be effective in reducing pterygium risk. The present findings suggest that circulating TC and LDL-c are risk factors for pterygium. Additionally, the results indicate that HMGCR inhibitors, which lower LDL-c levels, have a potential protective effect on pterygium outcomes. Further research is warranted to elucidate the underlying mechanisms involved in pterygium pathogenesis, with a particular focus on cholesterol metabolism. Research Network of Computational and Structural Biotechnology 2023-11-04 /pmc/articles/PMC10663701/ /pubmed/38022695 http://dx.doi.org/10.1016/j.csbj.2023.11.002 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Cai, Yuchen Fang, Fei Zhou, Tianyi Shi, Wenjun Cai, Xueyao Fu, Yao Genetic evidence implicating circulating lipids and lipid drug targets in pterygium |
title | Genetic evidence implicating circulating lipids and lipid drug targets in pterygium |
title_full | Genetic evidence implicating circulating lipids and lipid drug targets in pterygium |
title_fullStr | Genetic evidence implicating circulating lipids and lipid drug targets in pterygium |
title_full_unstemmed | Genetic evidence implicating circulating lipids and lipid drug targets in pterygium |
title_short | Genetic evidence implicating circulating lipids and lipid drug targets in pterygium |
title_sort | genetic evidence implicating circulating lipids and lipid drug targets in pterygium |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663701/ https://www.ncbi.nlm.nih.gov/pubmed/38022695 http://dx.doi.org/10.1016/j.csbj.2023.11.002 |
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