中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (5): 1302-1310.doi: 10.12307/2026.301

• 组织工程相关大数据分析 Big data analysis in tissue engineering • 上一篇    下一篇

甾醇酯增加骨质疏松病理性骨折风险：来自IEU-GWAS与芬兰数据库的证据

高增杰1，2，蒲  翔1，李来来1，柴艺汇1，黄  华 2，覃  裕2   

  1. 1贵州中医药大学基础医学院，贵州省贵阳市   550024；2北京积水潭医院贵州医院骨科，贵州省贵阳市   550017
  • 收稿日期:2025-01-17 接受日期:2025-04-03 出版日期:2026-02-18 发布日期:2025-06-28
  • 通讯作者: 蒲翔，教授，博士生导师，贵州中医药大学基础医学院，贵州省苗医药全省重点实验室，贵州省贵阳市 550024
  • 作者简介:高增杰，男，1986年生，山东省临沂市人，汉族，贵州中医药大学在读博士，主要从事中药、民族药配伍及药效学基础研究。
  • 基金资助:
    贵州省卫健委科学技术基金项目(gzwkj2025-364)，项目负责人：高增杰；贵州省苗医药全省重点实验室项目(黔科合平台[2025]018)，项目负责人：蒲翔

Increased risk of osteoporotic pathological fractures associated with sterol esters: evidence from IEU-GWAS and FinnGen databases

Gao Zengjie1, 2, Pu Xiang1, Li Lailai1, Chai Yihui1, Huang Hua2, Qin Yu2   

  1. 1School of Basic Medical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang 550024, Guizhou Province, China; 2Department of Orthopedics, Guizhou Hospital of Beijing Jishuitan Hospital, Guiyang 550017, Guizhou Province, China
  • Received:2025-01-17 Accepted:2025-04-03 Online:2026-02-18 Published:2025-06-28
  • Contact: Pu Xiang, Professor, Doctoral supervisor, School of Basic Medical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang 550024, Guizhou Province, China
  • About author:Gao Zengjie, MD candidate, School of Basic Medical Sciences, Guizhou University of Traditional Chinese Medicine, Guiyang 550024, Guizhou Province, China; Department of Orthopedics, Guizhou Hospital of Beijing Jishuitan Hospital, Guiyang 550017, Guizhou Province, China
  • Supported by:
    Science and Technology Fund of Guizhou Provincial Health Commission, No. gzwkj2025-364 (to GZJ); Guizhou Provincial Key Laboratory Project of Miao Medicine, No. [2025]018 (to PX)

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摘要：


文题释义：
甾醇酯：是一种脂质，主要形式是胆固醇酯，在血液中由胆固醇与脂肪酸合成。
单核苷酸多态性：指在基因组水平上由单个核苷酸的变异所引起的DNA序列多态性，是人类可遗传变异中最常见的一种，占所有已知多态性的90%以上。单核苷酸多态性在人类基因组中广泛存在，平均每几百个碱基对中就有1个，总数可达数百万个。单核苷酸多态性所表现的多态性只涉及单个碱基的变异，这种变异可能是转换或颠换。单核苷酸多态性既可能在基因序列内，也可能在基因以外的非编码序列上，对遗传性疾病研究具有重要意义。

背景：虽然研究发现脂质与骨质疏松病理性骨折风险之间存在一定的关联，但脂质水平与骨质疏松病理性骨折之间存在何种因果关系尚未明确。
目的：基于双样本双向孟德尔随机化分析明确脂质与骨质疏松病理性骨折之间的因果关系。
方法：从IEU-GWAS数据库(由英国布里斯托尔大学的MRC整合流行病学研究单元开发，提供大量全基因组关联研究汇总数据)获取178种脂质代谢物数据，从芬兰数据库(由芬兰国家基因研究项目构建，专注于芬兰人群基因组与健康、疾病关系的研究)获取骨质疏松病理性骨折数据(173 619名欧洲受试者)。将骨质疏松病理性骨折作为结局变量、脂质作为暴露因素，进行双向孟德尔随机化研究，评估不同脂质对骨质疏松病理性骨折的因果效应。将骨质疏松病理性骨折更换为英国生物样本数据库作为验证集，对结果进行横向验证。
结果与结论：①逆方差加权分析结果显示，甾醇酯(27:1/20:2)水平与骨质疏松病理性骨折存在显著的因果关联(OR=1.256，95%CI：1.001-1.575，P=0.049)，甾醇酯每增加一个单位，骨质疏松病理性骨折的风险增加约25.55%；反向孟德尔随机化分析结果显示，骨质疏松病理性骨折与磷脂酰胆碱、磷脂酰胆碱及磷脂酰胆碱水平呈显著负相关；横向验证结果显示甾醇酯是骨质疏松病理性骨折的危险因素。②结果显示甾醇酯是骨质疏松病理性骨折的危险因素，磷脂酰胆碱是骨质疏松病理性骨折的保护性因素，这些发现增加了脂质影响骨质疏松病理性骨折的证据，虽然研究采用的GWAS数据为欧洲样本来源，但鉴于人类遗传学的广泛共性，对中国人群通过调控血脂改善骨质疏松症具有重要的借鉴和参考意义。
https://orcid.org/0000-0003-4289-1625(高增杰) 

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 骨质疏松骨折, 脂质代谢, 甾醇酯, 孟德尔随机化, 骨折风险, 因果关联, 病理机制

Abstract: BACKGROUND: Although previous studies have reported associations between lipids and the risk of osteoporotic pathological fractures, the specific causal relationships between lipid level and osteoporotic pathological fractures remain unclear. 
OBJECTIVE: To elucidate the causal relationship between lipids and osteoporotic pathological fractures using a two-sample bidirectional Mendelian randomization analysis.
METHODS: The data for 178 lipid metabolites were obtained from the IEU-GWAS database (developed by the MRC Integrative Epidemiology Unit at the University of Bristol, UK, which provides extensive summary data from genome-wide association studies), while osteoporotic pathological fracture data (from 173 619 European participants) were acquired from the FinnGen database (constructed by the Finnish national gene research program, focusing on investigating relationships between genomics and health/disease in the Finnish population). Osteoporotic pathological fracture data were used as the outcome variable, with lipids serving as exposures, for the bidirectional Mendelian randomization study to evaluate the causal effects of different lipids on osteoporotic pathological fractures. The UK Biobank database was employed as a validation set by switching the outcome variable to verify the findings horizontally.
RESULTS AND CONCLUSION: (1) The inverse variance weighted analysis indicated that each unit increase in sterol ester (27:1/20:2) levels was associated with a 25.55% increase in the risk of osteoporotic pathological fractures (odds ratio=1.256, 95% confidence interval: 1.001-1.575, P = 0.049), suggesting a significant positive correlation between elevated sterol ester levels and increased fracture risk. Reverse Mendelian randomization analysis revealed a significant negative association between osteoporotic pathological fractures and three types of phosphatidylcholine. Horizontal validation yielded consistent results, confirming sterol ester as a risk factor for osteoporotic pathological fractures. (2) The results indicate that sterol ester is a risk factor for osteoporotic pathological fractures, while phosphatidylcholine serves as a protective factor. These findings strengthen the evidence supporting the effect of lipids on the risk of osteoporotic pathological fractures. Although the GWAS data used in this study were derived from European populations, given the broad commonality of human genetics, the results provide valuable reference significance for improving osteoporosis in Chinese populations through lipid regulation.

Key words: osteoporotic fracture, lipid metabolism, sterol ester, Mendelian randomization, fracture risk, causal association, pathological mechanism

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