Joint effects of atrial fibrillation and prothrombotic genotypes on the risk of venous thromboembolism

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis Pub Date : 2025-05-01 DOI:10.1016/j.rpth.2025.102880

Erin Mathiesen Hald , Maja–Lisa Løchen , Kristian Hveem , Mary Cushman , Sigrid K. Brækkan , John–Bjarne Hansen

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引用次数: 0

Abstract

Background

Atrial fibrillation (AF) is a risk factor for venous thromboembolism (VTE), but the role of common prothrombotic gene variants in this relationship is unknown.

Objectives

We investigated the joint effect of prothrombotic genotypes and AF on the risk of VTE in a population-based case-cohort.

Methods

Incident VTE cases (n = 1458) and a subcohort (n = 14,526) randomly sampled from the Tromsø (1994-2012) and Trøndelag Health (1995-2008) cohort studies were included. DNA was genotyped for rs8176719 (ABO), rs6025 (factor V Leiden [FVL]), rs1799963 (prothrombin), rs2066865 (fibrinogen gamma gene), and rs2036914 (F11). Hazard ratios (HRs) with 95% CIs for VTE were estimated by individual single-nucleotide polymorphisms and categories of a genetic risk score (0-1, 2, 3, 4, and ≥5 risk alleles) in subjects with and without AF.

Results

Over a median 12.3 years follow-up, 1421 participants were diagnosed with AF, of whom 139 developed subsequent VTE. Overall, participants with AF had a 1.7-fold increased risk of VTE (HR, 1.73; 95% CI, 1.43-2.08). Among those with AF, ≥1 risk allele of FVL was associated with 1.9-fold higher VTE risk (HR, 1.89; 95% CI, 1.13-3.17) compared with 0 risk alleles. None of the other single-nucleotide polymorphisms increased the risk. In participants without AF, the VTE risk increased linearly with increasing genetic risk score. No such association was found for those with AF.

Conclusion

We confirmed that AF is a risk factor for VTE and showed that this relationship was augmented for carriers of FVL. Other common prothrombotic genotypes do not add additional risk of VTE to that induced by AF alone.

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房颤和血栓前基因型对静脉血栓栓塞风险的共同影响

房颤（AF）是静脉血栓栓塞（VTE）的危险因素，但常见的血栓前基因变异在这一关系中的作用尚不清楚。目的：在以人群为基础的病例队列中，我们研究了血栓形成前基因型和房颤对静脉血栓栓塞风险的共同影响。方法从特罗姆瑟（1994-2012）和特朗德莱格健康（1995-2008）队列研究中随机抽取1458例静脉血栓栓塞病例和14526例亚队列。DNA分型为rs8176719 （ABO）、rs6025 （V Leiden因子[FVL]）、rs1799963（凝血酶原）、rs2066865（纤维蛋白原γ基因）和rs2036914 （F11）。通过个体单核苷酸多态性和遗传风险评分类别（0-1、2、3、4和≥5个风险等位基因）对有和没有房颤的受试者进行95% ci的风险比（hr）估计。结果在中位12.3年的随访中，1421名受试者被诊断为房颤，其中139人随后发展为房颤。总的来说，房颤患者发生静脉血栓栓塞的风险增加了1.7倍(HR, 1.73；95% ci, 1.43-2.08)。在房颤患者中，FVL风险等位基因≥1与VTE风险增加1.9倍相关(HR, 1.89；95% CI, 1.13-3.17)，与0风险等位基因相比。其他单核苷酸多态性都没有增加患病风险。在没有房颤的参与者中，静脉血栓栓塞的风险随着遗传风险评分的增加而线性增加。结论我们证实房颤是静脉血栓栓塞的一个危险因素，并且这种关系在FVL携带者中更为明显。其他常见的血栓前基因型并不会增加房颤单独诱发的静脉血栓栓塞的风险。

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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