中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (12): 2623-2630.doi: 10.12307/2025.391

• 组织构建相关数据分析 Date analysis of organization construction • 上一篇    下一篇

组织蛋白酶与骨密度的因果关系：双向孟德尔随机化分析

姜  楠1，符浩楠1，郝宇涵2，陈祉霖2，朱芷晴3，徐  峰4，于  栋4   

  1. 北京中医药大学，1第三临床医学院，2中医学院，北京市  100029；3安徽中医药大学，安徽省合肥市  230031；4北京中医药大学第三附属医院，北京市  100029
  • 收稿日期:2024-04-22 接受日期:2024-06-11 出版日期:2025-04-28 发布日期:2024-09-11
  • 通讯作者: 徐峰，博士，主任医师，硕士生导师，丹心计划博士生导师，北京中医药大学第三附属医院综合科，北京市 100029 共同通讯作者：于栋，博士，主任医师，硕士生导师，北京中医药大学第三附属医院脊柱科，北京市 100029
  • 作者简介:姜楠，女，1998年生，安徽省阜阳市人，汉族，北京中医药大学在读硕士，主要从事中医全科学方面的研究。
  • 基金资助:
    北京市教育科学规划课题项目(CDDB21167)，课题名称：以建立中医基层临床实践基地为导向开展中医临床本科教育全科方向的改革探索研究，项目负责人：徐峰

Causal association between cathepsins and bone mineral density: two-way Mendelian randomization analyses

Jiang Nan1, Fu Haonan1, Hao Yuhan2, Chen Zhilin2, Zhu Zhiqing3, Xu Feng4, Yu Dong4   

  1. 1The Third Clinical School of Beijing University of Chinese Medicine, Beijing 100029, China; 2College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; 3Anhui University of Chinese Medicine, Hefei 230031, Anhui Province, China; 4The Third Clinical Hospital of Beijing University of Chinese Medicine, Beijing 100029, China
  • Received:2024-04-22 Accepted:2024-06-11 Online:2025-04-28 Published:2024-09-11
  • Contact: Xu Feng, MD, Chief physician, Master’s supervisor, The Third Clinical Hospital of Beijing University of Chinese Medicine, Beijing 100029, China Co-corresponding author: Yu Dong, MD, Chief physician, Master’s supervisor, The Third Clinical Hospital of Beijing University of Chinese Medicine, Beijing 100029, China
  • About author:Jiang Nan, Master candidate, The Third Clinical School of Beijing University of Chinese Medicine, Beijing 100029, China
  • Supported by:
    Beijing Municipal Education Science Planning Project, No. CDDB21167 (to XF)

PDF

129

摘要：




文题释义：
孟德尔随机化：是一种以遗传变异为工具变量，遵循孟德尔定律，即相应的等位基因在胚胎形成时期随机分配且固定的原则，排除混杂因素对结果的影响，加强了因果推断证据的研究方法。
骨密度：又称骨骼矿物质密度，是指单位体积内骨矿物质(主要是钙和磷)的含量，单位为g/cm3，是反映骨骼强度的一个重要指标。

背景：既往研究表明，中老年人体内组织蛋白酶K水平可通过影响骨密度来干预骨质疏松的发生和发展，但组织蛋白酶家族与其他人群骨密度之间是否存在因果关系仍未知。
目的：探讨组织蛋白酶与骨密度的因果关系。
方法：从IEU Open GWAS数据库提取与8种组织蛋白酶相关的遗传位点作为工具变量，以5个年龄段人群的骨密度作为结局。通过双向孟德尔随机化分析，评估组织蛋白酶与骨密度的因果关系。使用Cochran’s Q检验评估遗传工具变量的异质性，使用MR-Egger截距检验评估多效性，使用留一法评估作为工具变量的单核苷酸多态性对暴露和结局因果关系影响的敏感性。
结果与结论：①正向孟德尔随机化的逆方差加权法结果显示，组织蛋白酶H与> 45岁且≤60岁人群的骨密度呈负相关[OR(95%CI)=
0.965(0.94-0.99)，P=0.04]，组织蛋白酶Z与> 30岁且≤45岁人群的骨密度呈负相关[OR(95% CI)=1.06(1.00-1.11)，P=0.03]；②敏感性分析结果显示因果关系稳定，MR-Egger截距分析未检测到潜在的水平多效性；③反向孟德尔随机化结果显示，骨密度对组织蛋白酶无显著反向作用；④上述结果证实，组织蛋白酶对部分年龄段人群骨密度会造成影响，可能会增加骨质疏松症的发病风险，应给予更多关注。

https://orcid.org/0009-0000-4161-4939(姜楠)

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 骨密度, 组织蛋白酶, 孟德尔随机化, 因果关联, 不同年龄段

Abstract: BACKGROUND: Previous studies have indicated that cathepsin K can intervene with the occurrence and development of osteoporosis by regulating bone mineral density in middle-aged and older adults. However, whether there is a causal relationship between the cathepsin family and bone mineral density in other populations remains unknown.
OBJECTIVE: To investigate the causal relationship between cathepsin and bone mineral density.
METHODS: Genetic loci associated with eight cathepins were extracted from the IEU Open GWAS database as instrumental variables, and bone mineral density values in five age groups acted as an outcome. The causal relationship between cathepin and bone mineral density was assessed by two-way Mendelian randomization analysis. Heterogeneity of the genetic instrumental variables was assessed using Cochran’s Q test, pleiotropy was assessed using the MR-Egger intercept test, and the sensitivity of single nucleotide polymorphisms used as instrumental variables to the causal effect of exposure and outcome was assessed using the leave-one-out method.
RESULTS AND CONCLUSION: The results of the inverse variance weighting method with positive Mendelian randomization showed that cathepin H was negatively associated with bone mineral density in people aged 45-60 years [odds ratio (95% confidence interval)=0.965(0.94-0.99), P=0.04]; cathepin Z was negatively associated with bone mineral density in people aged 30-45 year [odds ratio (95% confidence interval)=1.06 (1.00-1.11), P=0.03]. The results of sensitivity analysis showed a stable causal relationship, and MR-Egger intercept analysis did not detect potential horizontal pleiotropy. The inverse Mendelian randomization results showed that bone mineral density had no significant inverse effect on cathepin. The above results confirm that cathepin can affect bone mineral density in some age groups, which may increase the risk of osteoporosis and should be given more attention.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: bone mineral density, cathepsin, Mendelian randomization, causal association, different age groups

中图分类号: