中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (11): 2909-2919.doi: 10.12307/2026.093

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

胰岛素样生长因子与缺血性脑卒中：基于欧洲人群全基因组的关联分析

周欣滢1，孙新月2，朱文浩2   

  1. 1山东中医药大学，山东省济南市   250355；2淄博市中医医院，山东省淄博市   255399
  • 收稿日期:2025-02-05 接受日期:2025-05-30 出版日期:2026-04-18 发布日期:2025-09-10
  • 通讯作者: 朱文浩，硕士生导师，主任医师，淄博市中医医院，山东省淄博市 255399
  • 作者简介:周欣滢，女，2001年生，山东省淄博市人，汉族，山东中医药大学2024级硕士，主要从事中医脑系疾病研究。
  • 基金资助:
    第五批全国中医临床优秀人才研修项目(国中医药人教函[2022]1号)，项目负责人：朱文浩；国家中医药管理局科技司共建科技项目(GZY-KJS-SD-2023-008)，项目负责人：朱文浩

Insulin-like growth factors and ischemic stroke: a genome-wide association analysis in European populations

Zhou Xinying1, Sun Xinyue2, Zhu Wenhao2   

  1. 1Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China; 2Zibo Hospital of Traditional Chinese Medicine, Zibo 255399, Shandong Province, China
  • Received:2025-02-05 Accepted:2025-05-30 Online:2026-04-18 Published:2025-09-10
  • Contact: Zhu Wenhao, Master’s supervisor, Chief physician, Zibo Hospital of Traditional Chinese Medicine, Zibo 255399, Shandong Province, China
  • About author:Zhou Xinying, MS candidate, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
  • Supported by:
    The Fifth Batch of National Training Program for Clinical Excellence in Traditional Chinese Medicine, No. [2022]1 (to ZWH); Science and Technology Co-construction Project of Science and Technology Department of the State Administration of Traditional Chinese Medicine, No. GZY-KJS-SD-2023-008 (to ZWH)

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摘要：


文题释义：
胰岛素样生长因子：是人体内关键的促生长肽，既是内分泌激素又是自分泌/旁分泌生长因子，在人体正常生理状态方面发挥着重要作用，包括生长发育、伤口愈合、调节代谢、神经保护等，同时也与多种疾病的发生有关。
孟德尔随机化：是一种工具变量分析形式，具有快速高效、成本低、可行性高等优点。孟德尔随机化充分利用已发表的全基因组关联研究(GWAS)数据结果，使用遗传变异作为工具变量进行因果推断，能够有效克服传统流行病学研究的混杂偏差，避免潜在混杂因素的影响。

背景：近年来越来越多的研究证据显示，胰岛素样生长因子可能与缺血性脑卒中存在密切联系，然而，胰岛素样生长因子与缺血性脑卒中及其亚型之间的因果关系尚不明确。
目的：利用孟德尔随机化分析探究胰岛素样生长因子与缺血性脑卒中及其亚型的因果关联。
方法：从IEU OpenGWAS数据库(由英国布里斯托尔大学的MRC综合流行病学单位开发，专注于整合流行病学、遗传学和生物统计学数据)获取胰岛素样生长因子全基因组关联研究数据，从MEGASTROKE数据库(由国际卒中遗传学联盟发起的一项合作，旨在荟萃分析脑卒中及其亚型的全基因组关联研究数据)获取缺血性脑卒中及其亚型(大动脉脑卒中、心源性脑卒中、小血管脑卒中)全基因组关联研究数据。针对14种胰岛素样生长因子和缺血性脑卒中及其亚型进行双向孟德尔随机化分析，采用逆方差加权法作为主要统计方法，利用Cochran’s Q检验和MR-Egger回归分析评价结果的多效性和异质性。
结果与结论：①正向孟德尔随机化分析结果显示，各胰岛素样生长因子与缺血性脑卒中、大动脉脑卒中、小血管脑卒中的发病风险之间均不存在显著的因果关联(P均> 0.05)，胰岛素样生长因子结合蛋白7与心源性脑卒中的发病风险呈负向因果关系(OR=0.82，95%CI=0.74-0.91，P=0.006)，胰岛素样生长因子结合蛋白7属于心源性脑卒中的保护因素。反向孟德尔随机化分析结果显示，缺血性脑卒中、大动脉脑卒中、心源性脑卒中、小血管脑卒中与胰岛素样生长因子均不存在反向因果关系。②研究结果提供了胰岛素样生长因子与缺血性脑卒中及其亚型之间的流行病学证据，强调了胰岛素样生长因子在缺血性脑卒中各型发病、发展等方面的潜在作用，为中国人群缺血性脑卒中与胰岛素样生长因子的相关研究提供了借鉴，有助于理解缺血性脑卒中的病理机制，提供预防、治疗等方面的新思路。
https://orcid.org/0009-0000-0010-211X (周欣滢) 

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: 胰岛素样生长因子, 缺血性脑卒中, 大动脉脑卒中, 心源性脑卒中, 小血管脑卒中, 孟德尔随机化, 因果关系, 工程化组织构建

Abstract: BACKGROUND: In recent years, increasing evidence has shown that insulin-like growth factors may be associated with ischemic stroke. However, the causal association between insulin-like growth factors and ischemic stroke and its subtypes remain unclear.
OBJECTIVE: To explore the causal association between insulin-like growth factors and ischemic stroke and its subtypes by Mendelian randomization.
METHODS: We obtained genome-wide association study (GWAS) data for insulin-like growth factor from the IEU OpenGWAS database (developed by the MRC Integrative Epidemiology Unit at the University of Bristol, UK, which focuses on integrating data from epidemiology, genetics, and biostatistics), and acquired GWAS data for ischemic stroke and its subtypes (large artery stroke, cardioembolic stroke, and small vessel stroke) from the MEGASTROKE database (a collaborative initiative by the International Stroke Genetics Consortium aimed at meta-analyzing GWAS data for stroke and its subtypes). We performed two-way Mendelian randomization analysis to explore the causal association between 14 insulin-like growth factors and ischemic stroke and its subtypes. The inverse variance weighted method was used as the main statistical method. Cochran’s Q test and MR-Egger regression were used to evaluate the pleiotropy and heterogeneity.
RESULTS AND CONCLUSION: (1) Results of the forward Mendelian randomization analysis showed no significant causal association between any insulin-like growth factors and the risk of ischemic stroke, large artery stroke, or small vessel stroke (all P > 0.05). However, insulin-like growth factor-binding protein 7 exhibited a negative causal relationship with cardioembolic stroke (odds ratio=0.82, 95% confidence interval=0.74–0.91, P=0.006), indicating that insulin-like growth factor-binding protein 7 is a protective factor against cardioembolic stroke. Results of the reverse Mendelian randomization analysis revealed no reverse causal relationship between ischemic stroke, large artery stroke, cardioembolic stroke, or small vessel stroke and insulin-like growth factors. (2) The findings provide epidemiological evidence on the association between insulin-like growth factors and ischemic stroke and its subtypes, highlighting the potential role of insulin-like growth factors in the pathogenesis and progression of different stroke subtypes. This study offers valuable insights for research on insulin-like growth factors and ischemic stroke in Chinese populations, contributing to a deeper understanding of the pathological mechanisms underlying ischemic stroke and suggesting novel perspectives for its prevention and treatment.

Key words: insulin-like growth factors, ischemic stroke, large artery stroke, cardioembolic stroke, small vessel stroke, Mendelian randomization, causality, engineered tissue construction

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