Hald Erin Mathiesen, Løchen Maja-Lisa, Mathiesen Ellisiv B, Hveem Kristian, Brækkan Sigrid K, Hansen John-Bjarne
Thrombosis Research Group, Department of Clinical Medicine, UiT The Arctic University of North Norway, Tromsø, Norway; Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
Epidemiology of Chronic Diseases Research Group, Department of Community Medicine, UiT The Arctic University of North Norway, Tromsø, Norway.
J Thromb Haemost. 2025 Apr;23(4):1401-1406. doi: 10.1016/j.jtha.2024.12.022. Epub 2024 Dec 31.
Atrial fibrillation (AF) is a major risk factor for ischemic stroke. Whether prothrombotic single nucleotide polymorphisms (SNPs) impact stroke risk in AF is not well known.
To investigate the joint effects of 5 prothrombotic SNPs and AF on ischemic stroke risk.
A subcohort (n = 14 583) was randomly sampled from the Tromsø (1994-2012) and the Trøndelag Health (1995-2008) studies. DNA was genotyped for rs8176719 (ABO blood type), rs6025 (factor [F]V Leiden), rs1799963 (prothrombin G20210A), rs2066865 (fibrinogen-γ), and rs2036914 (F11). Hazard ratios (HRs) with 95% CIs for incident ischemic stroke were estimated by AF status for individual SNPs and by categories of a genetic risk score.
A total of 1091 participants developed AF during follow-up, of whom 169 (15.5%) subsequently had a stroke. Having ≥1 risk allele in prothrombin, FV Leiden, F11, or fibrinogen-γ was not associated with excess stroke risk in AF. In the absence of AF, ≥1 risk allele(s) in ABO was not associated with stroke (HR, 1.03; 95% CI, 0.85-1.25), whereas those with AF and ≥1 risk allele(s) in ABO had a 1.4-fold increased stroke risk compared with those with AF and no risk allele (HR, 1.42; 95% CI, 0.99-2.04). There was no linear increase in stroke risk across categories of the genetic risk score in participants either with or without AF.
Most prothrombotic SNPs were not associated with ischemic stroke risk, regardless of AF status. The ABO SNP was associated with ischemic stroke risk in those with AF only.
心房颤动（AF）是缺血性卒中的主要危险因素。促血栓形成单核苷酸多态性（SNP）是否影响AF患者的卒中风险尚不清楚。
研究5种促血栓形成SNP与AF对缺血性卒中风险的联合作用。
从特罗姆瑟（1994 - 2012年）和特伦德拉格健康（1995 - 2008年）研究中随机抽取一个亚队列（n = 14583）。对rs8176719（ABO血型）、rs6025（因子[F]V Leiden）、rs1799963（凝血酶原G20210A）、rs2066865（纤维蛋白原-γ）和rs2036914（F11）进行DNA基因分型。通过个体SNP以及遗传风险评分类别，根据AF状态估计发生缺血性卒中的风险比（HR）及95%置信区间（CI）。
共有1091名参与者在随访期间发生AF，其中169名（15.5%）随后发生卒中。凝血酶原、F V Leiden、F11或纤维蛋白原-γ中存在≥1个风险等位基因与AF患者卒中风险增加无关。在无AF的情况下，ABO中存在≥1个风险等位基因与卒中无关（HR，1.03；95%CI，0.85 - 1.25），而AF患者且ABO中存在≥1个风险等位基因的患者与无风险等位基因的AF患者相比，卒中风险增加1.4倍（HR，1.4±2；95%CI，0.99 - 2.04）。无论有无AF，参与者的遗传风险评分类别与卒中风险均无线性增加关系。
无论AF状态如何，大多数促血栓形成SNP与缺血性卒中风险无关。ABO SNP仅与AF患者的缺血性卒中风险相关。
