Department of Clinical Biochemistry, Herlev Hospital, and the Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
CMAJ. 2013 Mar 19;185(5):E229-37. doi: 10.1503/cmaj.121636. Epub 2013 Feb 4.
ABO blood type locus has been reported to be an important genetic determinant of venous and arterial thrombosis in genome-wide association studies. We tested the hypothesis that ABO blood type alone and in combination with mutations in factor V Leiden R506Q and prothrombin G20210A is associated with the risk of venous thromboembolism and myocardial infarction in the general population.
We used data from 2 Danish studies that followed members of the general public from 1977 through 2010. We obtained the genotype of 66 001 white participants for ABO blood type, factor V Leiden R506Q and prothrombin G20210A. We calculated hazard ratios (HRs) and population attributable risk. Our main outcome measures were venous thromboembolism and myocardial infarction.
The multivariable adjusted HR for venous thromboembolism was 1.4 (95% confidence interval [CI] 1.3-1.5) for non-O blood type (v. O blood type). For the factor V Leiden R506Q mutation, the adjusted HR was 2.2 (95% CI 2.0-2.5) for heterozygous participants and 7.0 (95%CI 4.8-10) for homozygous participants (v. participants without the mutation). For prothrombin G20210A, the adjusted HR was 1.5 (95%CI 1.2-1.9) for heterozygous participants and 11 (95% CI 2.8-44) for homozygous participants (v. participants without the mutation). When we combined ABO blood type and factor V Leiden R506Q or prothrombin G20210A genotype, there was a stepwise increase in the risk of venous thromboembolism (trend, p<0.001). The population attributable risk of venous thromboembolism was 20% for ABO blood type, 10% for factor V Leiden R506Q and 1% for prothrombin G20210A. Multivariable adjusted HRs for myocardial infarction by genotypes did not differ from 1.0.
ABO blood type had an additive effect on the risk of venous thromboembolism when combined with factor V Leiden R506Q and prothrombin G20210A mutations; blood type was the most important risk factor for venous thromboembolism in the general population.
ABO 血型基因座已被报道是全基因组关联研究中静脉血栓和动脉血栓形成的重要遗传决定因素。我们检验了如下假说，即 ABO 血型单独以及与因子 V 莱顿 R506Q 和凝血酶原 G20210A 突变联合，与普通人群静脉血栓栓塞和心肌梗死的风险相关。
我们使用了两项丹麦研究的数据，这些研究从 1977 年至 2010 年期间对普通公众成员进行了随访。我们获得了 66001 名白人参与者的 ABO 血型、因子 V 莱顿 R506Q 和凝血酶原 G20210A 的基因型。我们计算了危险比（HRs）和人群归因风险。我们的主要结局指标是静脉血栓栓塞和心肌梗死。
非 O 血型（与 O 血型相比）的多变量校正静脉血栓栓塞 HR 为 1.4（95%置信区间[CI]1.3-1.5）。对于因子 V 莱顿 R506Q 突变，杂合子参与者的校正 HR 为 2.2（95%CI2.0-2.5），纯合子参与者为 7.0（95%CI4.8-10）（与无突变参与者相比）。对于凝血酶原 G20210A，杂合子参与者的校正 HR 为 1.5（95%CI1.2-1.9），纯合子参与者为 11（95%CI2.8-44）（与无突变参与者相比）。当我们将 ABO 血型与因子 V 莱顿 R506Q 或凝血酶原 G20210A 基因型相结合时，静脉血栓栓塞的风险呈逐步增加（趋势，p<0.001）。ABO 血型导致静脉血栓栓塞的人群归因风险为 20%，因子 V 莱顿 R506Q 为 10%，凝血酶原 G20210A 为 1%。根据基因型，多变量校正心肌梗死的 HR 与 1.0 无差异。
ABO 血型与因子 V 莱顿 R506Q 和凝血酶原 G20210A 突变联合时，对静脉血栓栓塞的风险具有附加效应；血型是普通人群静脉血栓栓塞的最重要危险因素。
