Jacob Odeberg, MD PhD, Department of Proteomics, School of Biotechnology, Royal Institute of Technology (KTH), Science for Life Laboratory Stockholm, Box 1031, 171 21 Solna, Sweden, Tel: +46 70 2087571, Fax: +46 8 51775084, Email:
Thromb Haemost. 2016 Jan;115(2):406-14. doi: 10.1160/TH15-06-0459. Epub 2015 Oct 1.
Genetic associations for the reoccurrence of venous thromboembolism (VTE) are not well described. Our aim was to investigate if common genetic variants, previously found to contribute to the prediction of first time thrombosis in women, were associated with risk of recurrence. The Thromboembolism Hormone Study (TEHS) is a Swedish nationwide case-control study (2002-2009). A cohort of 1,010 women with first time VTE was followed up until a recurrent event, death or November 2011. The genetic variants in F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446 were assessed together with clinical variables. Recurrence rate was calculated as the number of events over the accumulated patient-time. Cumulative recurrence was calculated by Kaplan-Meier curve. Cox proportional-hazard model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between groups. A total of 101 recurrent events occurred during a mean follow-up time of five years. The overall recurrence rate was 20 per 1,000 person-years (95% CI; 16-24). The recurrence rate was highest in women with unprovoked first event and obesity. Carriers of the risk alleles of F5 rs6025 (HR=1.7 (95% CI; 1.1-2.6)) and F11 rs2289252 (HR=1.8 (95% CI; 1.1-3.0)) had significantly higher rates of recurrence compared to non-carriers. The cumulative recurrence was 2.5-fold larger in carriers of both F5 rs6025 and F11 rs2289252 than in non-carriers at five years follow-up. In conclusion, F5 rs6025 and F11 rs2289252 contributed to the risk of recurrent VTE and the combination is of potential clinical relevance for risk prediction.
遗传因素与静脉血栓栓塞症（VTE）的复发有关，但目前尚不清楚。我们的目的是研究先前发现与女性首次血栓形成预测相关的常见遗传变异是否与复发风险相关。血栓形成激素研究（TEHS）是一项瑞典全国范围内的病例对照研究（2002-2009 年）。一组 1010 名首次发生 VTE 的女性患者在随访期间出现复发事件、死亡或 2011 年 11 月。评估了 F5 rs6025、F2 rs1799963、ABO rs514659、FGG rs2066865、F11 rs2289252、PROC rs1799810 和 KNG1 rs710446 等遗传变异与临床变量之间的关系。复发率计算为事件数与累积患者时间的比值。通过 Kaplan-Meier 曲线计算累积复发率。使用 Cox 比例风险模型估计组间风险比（HR）和 95%置信区间（95%CI）。平均随访 5 年后共发生 101 例复发事件。总复发率为 20/1000 人年（95%CI：16-24）。首次无诱因事件和肥胖女性的复发率最高。F5 rs6025 风险等位基因携带者（HR=1.7（95%CI：1.1-2.6））和 F11 rs2289252（HR=1.8（95%CI：1.1-3.0））的复发率明显高于非携带者。F5 rs6025 和 F11 rs2289252 携带者的累积复发率在 5 年随访时是非携带者的 2.5 倍。总之，F5 rs6025 和 F11 rs2289252 增加了 VTE 复发的风险，这种联合可能对风险预测具有潜在的临床意义。
