{"title":"血脂和降脂药物靶基因与骨髓炎之间的关系：孟德尔随机分析","authors":"Zhiyi Zhou, Zhehan Yang, Junpan Chen, Minghao Wen, Jiayuan Lei, Wanzhe Liao, Yahan Li, Linghui Liu, Ziyuan Lu","doi":"10.1002/med4.70009","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Lipid metabolism is a key regulator of inflammation in acute and chronic conditions. However, whether dyslipidemia is related to the process of osteomyelitis remains unclear. This study aimed to use a Mendelian randomization (MR) analysis to examine the associations between triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and osteomyelitis. Additionally, the associations between the genes corresponding to these traits and osteomyelitis were investigated.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Genetic variants associated with TG and TC were selected from the Global Lipids Genetics Consortium, while LDL-C datasets were extracted from the UK Biobank. Specifically, the lipid-lowering drug target regions were selected as proxies for drug target perturbation. Osteomyelitis was identified according to the FinnGen consortium. We also conducted supplementary analyses using C-reactive protein genome-wide association study data to examine the effect of drug targets on this inflammatory marker. Furthermore, we conducted mediation analyses focusing on several risk factors for osteomyelitis.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>No association was found between LDL-C, TG, or TC concentrations and osteomyelitis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was significantly associated with a lower risk of osteomyelitis (odds ratio [95% confidence interval] = 0.49 [0.32–0.76], <i>p</i> = 1.60 × 10<sup>−3</sup>) and a lower concentration of C-reactive protein (0.94 [0.92–0.97], <i>p</i> = 3.16 × 10<sup>−4</sup>). We found that waist circumference was an intermediate variable between PCSK9 and osteomyelitis.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>This study does not support a relationship between dyslipidemia and osteomyelitis. PCSK9 is associated with a lower risk of osteomyelitis. Our findings suggest that waist circumference is a potential mediator between osteomyelitis and PCSK9. Additionally, PCSK9 is associated with reduced CRP concentrations.</p>\n </section>\n </div>","PeriodicalId":100913,"journal":{"name":"Medicine Advances","volume":"3 2","pages":"80-87"},"PeriodicalIF":0.0000,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med4.70009","citationCount":"0","resultStr":"{\"title\":\"Associations Between Lipids and Lipid-Lowering Drug Target Genes and Osteomyelitis: A Mendelian Randomization Analysis\",\"authors\":\"Zhiyi Zhou, Zhehan Yang, Junpan Chen, Minghao Wen, Jiayuan Lei, Wanzhe Liao, Yahan Li, Linghui Liu, Ziyuan Lu\",\"doi\":\"10.1002/med4.70009\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Lipid metabolism is a key regulator of inflammation in acute and chronic conditions. However, whether dyslipidemia is related to the process of osteomyelitis remains unclear. This study aimed to use a Mendelian randomization (MR) analysis to examine the associations between triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and osteomyelitis. Additionally, the associations between the genes corresponding to these traits and osteomyelitis were investigated.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Genetic variants associated with TG and TC were selected from the Global Lipids Genetics Consortium, while LDL-C datasets were extracted from the UK Biobank. Specifically, the lipid-lowering drug target regions were selected as proxies for drug target perturbation. Osteomyelitis was identified according to the FinnGen consortium. We also conducted supplementary analyses using C-reactive protein genome-wide association study data to examine the effect of drug targets on this inflammatory marker. Furthermore, we conducted mediation analyses focusing on several risk factors for osteomyelitis.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>No association was found between LDL-C, TG, or TC concentrations and osteomyelitis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was significantly associated with a lower risk of osteomyelitis (odds ratio [95% confidence interval] = 0.49 [0.32–0.76], <i>p</i> = 1.60 × 10<sup>−3</sup>) and a lower concentration of C-reactive protein (0.94 [0.92–0.97], <i>p</i> = 3.16 × 10<sup>−4</sup>). We found that waist circumference was an intermediate variable between PCSK9 and osteomyelitis.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>This study does not support a relationship between dyslipidemia and osteomyelitis. PCSK9 is associated with a lower risk of osteomyelitis. Our findings suggest that waist circumference is a potential mediator between osteomyelitis and PCSK9. Additionally, PCSK9 is associated with reduced CRP concentrations.</p>\\n </section>\\n </div>\",\"PeriodicalId\":100913,\"journal\":{\"name\":\"Medicine Advances\",\"volume\":\"3 2\",\"pages\":\"80-87\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-04-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med4.70009\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Medicine Advances\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/med4.70009\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medicine Advances","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/med4.70009","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Associations Between Lipids and Lipid-Lowering Drug Target Genes and Osteomyelitis: A Mendelian Randomization Analysis
Background
Lipid metabolism is a key regulator of inflammation in acute and chronic conditions. However, whether dyslipidemia is related to the process of osteomyelitis remains unclear. This study aimed to use a Mendelian randomization (MR) analysis to examine the associations between triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and osteomyelitis. Additionally, the associations between the genes corresponding to these traits and osteomyelitis were investigated.
Methods
Genetic variants associated with TG and TC were selected from the Global Lipids Genetics Consortium, while LDL-C datasets were extracted from the UK Biobank. Specifically, the lipid-lowering drug target regions were selected as proxies for drug target perturbation. Osteomyelitis was identified according to the FinnGen consortium. We also conducted supplementary analyses using C-reactive protein genome-wide association study data to examine the effect of drug targets on this inflammatory marker. Furthermore, we conducted mediation analyses focusing on several risk factors for osteomyelitis.
Results
No association was found between LDL-C, TG, or TC concentrations and osteomyelitis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was significantly associated with a lower risk of osteomyelitis (odds ratio [95% confidence interval] = 0.49 [0.32–0.76], p = 1.60 × 10−3) and a lower concentration of C-reactive protein (0.94 [0.92–0.97], p = 3.16 × 10−4). We found that waist circumference was an intermediate variable between PCSK9 and osteomyelitis.
Conclusions
This study does not support a relationship between dyslipidemia and osteomyelitis. PCSK9 is associated with a lower risk of osteomyelitis. Our findings suggest that waist circumference is a potential mediator between osteomyelitis and PCSK9. Additionally, PCSK9 is associated with reduced CRP concentrations.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
