Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Cai, Yuchen, Fang, Fei, Zhou, Tianyi, Shi, Wenjun, Cai, Xueyao, Fu, Yao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Research Network of Computational and Structural Biotechnology 2023
Materias:
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
_version_ 1785138457448808448
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
work_keys_str_mv AT caiyuchen geneticevidenceimplicatingcirculatinglipidsandlipiddrugtargetsinpterygium
AT fangfei geneticevidenceimplicatingcirculatinglipidsandlipiddrugtargetsinpterygium
AT zhoutianyi geneticevidenceimplicatingcirculatinglipidsandlipiddrugtargetsinpterygium
AT shiwenjun geneticevidenceimplicatingcirculatinglipidsandlipiddrugtargetsinpterygium
AT caixueyao geneticevidenceimplicatingcirculatinglipidsandlipiddrugtargetsinpterygium
AT fuyao geneticevidenceimplicatingcirculatinglipidsandlipiddrugtargetsinpterygium