Genome-wide association studies in chronic venous disease: A systematic review

IF 3.1 2区医学 Q2 PERIPHERAL VASCULAR DISEASE

Journal of vascular surgery. Venous and lymphatic disorders Pub Date : 2026-03-01 Epub Date: 2025-12-13 DOI:10.1016/j.jvsv.2025.102365

Chien Lin Soh MBBChir, MA(Cantab), MRCS, Matthew Tan MBBS, BSc(Hons), PhD, MRCS, FHEA, Alun H. Davies DM, FRCS, MA, DSc, FHEA, FEBVS, FACPH, BM, BCh, Sarah Onida BSc(Hons), MD, PhD, FRCS

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引用次数: 0

Abstract

Background

Chronic venous disease (CVD) arises from venous hypertension secondary to impaired venous return, causing significant morbidity and diminished quality of life. Genetic factors are likely important in the pathogenesis and susceptibility of a patient to develop CVD. This systematic review summarizes genome-wide association studies (GWASs) that investigate the link between genetic variants and CVD.

Methods

A systematic review was conducted in accordance with the PRISMA guidelines, with the search dates ranging from January 1, 1994, to July 17, 2025. Abstract and full-text screening were completed by two independent reviewers, with any conflicts referred to a third senior reviewer. GWASs in adults investigating links between genetic variants and CVD were included. Exclusion criteria included patients with venous thromboembolism, arterial or diabetic disease, or animal models.

Results

Thirteen studies were included after screening 517 studies from a search of PubMed, EMBASE, and Ovid. Database sources included UK Biobank, FinnGen, PopGen, and country- or hospital-specific databases with a majority Caucasian and European patient cohort. A total of 602,760 patients were identified with varicose veins and 3,664,604 control cases that were studied with GWASs and other statistical methods including a two-sample Mendelian randomization approach, functional mapping, and genetic correlations. A variety of statistically significant genetic polymorphisms were identified that can be attributed to the heritability of varicose veins affecting inflammation and immunity (eg, PPP3R1, EBF1, and GATA2), hypertension (eg, CASZ1), and vascular architecture (eg, CASZ1, PIEZO1, and STIM2). Protective variants (eg, GJD3, MMP10, and 4EBP1) were also identified in Finnish populations. However, replication studies showed that these genetic polymorphisms are not generalizable to specific populations.

Conclusions

This systematic review highlights genes contributing to the development of CVD that have been identified in the literature. An improved understanding of genetic contributions to the pathogenesis of CVD may inform future diagnostics, prognostics, and personalized treatment. Further larger scale studies representative of global populations, including meta-analyses of genome-wide association datasets, are required owing to individual GWASs being statistically insufficient to draw generalizable conclusions.

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慢性静脉疾病的全基因组关联研究（GWAS）：系统综述

背景：慢性静脉疾病（CVD）是由继发于静脉回流受损的静脉高压引起的，可引起显著的发病率和生活质量下降。遗传因素可能是重要的发病机制和易感性的病人发展心血管疾病。这篇系统综述总结了研究遗传变异和心血管疾病之间联系的全基因组关联研究。方法：按照系统评价和荟萃分析首选报告项目（PRISMA）进行系统评价，检索日期为1994年1月1日至2025年7月17日。摘要和全文筛选由两名独立审稿人完成，任何冲突提交给第三名高级审稿人。研究基因变异与心血管疾病之间关系的成人GWAS研究也包括在内。排除标准包括静脉血栓栓塞、动脉或糖尿病疾病患者或动物模型。结果：从PubMed、EMBASE和Ovid检索中筛选517项研究后，纳入13项研究。数据库来源包括UK Biobank， FinnGen， PopGen和国家或医院特定数据库，其中大多数是高加索和欧洲患者队列。通过GWAS和其他统计方法（包括双样本孟德尔随机化方法、功能作图和遗传相关性）研究了602760例静脉曲张患者和3664604例对照病例。我们发现了多种具有统计学意义的遗传多态性，可归因于影响炎症和免疫的静脉曲张（如PPP3R1、EBF1、GATA2）、高血压（如CASZ1）和血管结构（如CASZ1、PIEZO1、STIM2）的遗传性。在芬兰人群中也发现了保护性变异（如GJD3、MMP10、4EBP1）。然而，复制研究表明，这些遗传多态性并不适用于特定人群。结论：本系统综述突出了文献中已确定的与心血管疾病发展有关的基因。提高对CVD发病机制的遗传贡献的理解可能为未来的诊断、预后和个性化治疗提供信息。由于单个GWASs在统计上不足以得出可推广的结论，因此需要进一步开展具有全球人群代表性的更大规模研究，包括全基因组关联数据集的荟萃分析。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of vascular surgery. Venous and lymphatic disorders SURGERYPERIPHERAL VASCULAR DISEASE&n-PERIPHERAL VASCULAR DISEASE

CiteScore

6.30

自引率

18.80%

发文量

328

审稿时长

71 days

期刊介绍： Journal of Vascular Surgery: Venous and Lymphatic Disorders is one of a series of specialist journals launched by the Journal of Vascular Surgery. It aims to be the premier international Journal of medical, endovascular and surgical management of venous and lymphatic disorders. It publishes high quality clinical, research, case reports, techniques, and practice manuscripts related to all aspects of venous and lymphatic disorders, including malformations and wound care, with an emphasis on the practicing clinician. The journal seeks to provide novel and timely information to vascular surgeons, interventionalists, phlebologists, wound care specialists, and allied health professionals who treat patients presenting with vascular and lymphatic disorders. As the official publication of The Society for Vascular Surgery and the American Venous Forum, the Journal will publish, after peer review, selected papers presented at the annual meeting of these organizations and affiliated vascular societies, as well as original articles from members and non-members.