Wiggins K L, Smith N L, Glazer N L, Rosendaal F R, Heckbert S R, Psaty B M, Rice K M, Lumley T
Department of Medicine, University of Washington, Seattle, WA 98101, USA.
J Thromb Haemost. 2009 Feb;7(2):263-9. doi: 10.1111/j.1538-7836.2008.03243.x. Epub 2008 Nov 25.
The non-O alleles of the ABO genotype have been associated with an increased risk of thrombosis. Risk associated with the specific A(1), A(2) or B alleles is not well defined.
To examine the association of the ABO genotype with myocardial infarction (MI), ischemic stroke, hemorrhagic stroke, and venous thrombosis (VT).
We used data from two ongoing population-based case-control studies of MI, stroke, and VT. Cases included hypertensive adults and postmenopausal women with incident non-fatal MI (n = 1063), ischemic stroke (n = 469), and hemorrhagic stroke (n = 91), and postmenopausal women with incident non-fatal VT (n = 504). Controls were frequency matched to cases on age, sex, hypertension status, and year of identification. ABO genotypes were determined using single-nucleotide polymorphisms, and subjects were grouped by diplotype according to the presence of O(1), O(2), A(11), A(2) and B alleles. Logistic regression was used to test the association of diplotypes with risk of each outcome.
As compared with the O(1)O(1) group, the A(11) allele was associated with an increased risk of VT [odds ratio (OR) 1.79; 95% confidence interval (CI) 1.41-2.26] and MI (OR 1.23; 95% CI 1.05-1.44). The B allele was associated with an increased risk of VT (OR 1.82; 95% CI 1.29-2.57) and ischemic stroke (OR 1.59; 95% CI 1.17-2.17). The AB diplotype category was associated with a 2.7-fold risk of VT (OR 2.70; 95% CI 1.73-4.21). No other associations reached significance.
The VT and MI findings are confirmatory, and the ischemic stroke finding with the B allele is a novel finding and needs replication.
ABO基因型的非O等位基因与血栓形成风险增加有关。与特定的A(1)、A(2)或B等位基因相关的风险尚未明确界定。
研究ABO基因型与心肌梗死(MI)、缺血性卒中、出血性卒中和静脉血栓形成(VT)之间的关联。
我们使用了两项正在进行的基于人群的MI、卒中和VT病例对照研究的数据。病例包括患有非致死性MI(n = 1063)、缺血性卒中(n = 469)和出血性卒中(n = 91)的高血压成年人及绝经后女性,以及患有非致死性VT(n = 504)的绝经后女性。对照在年龄、性别、高血压状态和识别年份方面与病例进行频率匹配。使用单核苷酸多态性确定ABO基因型,并根据O(1)、O(2)、A(11)、A(2)和B等位基因的存在情况将受试者按双倍型分组。使用逻辑回归检验双倍型与每种结局风险之间的关联。
与O(1)O(1)组相比,A(11)等位基因与VT风险增加相关[比值比(OR)1.79;95%置信区间(CI)1.41 - 2.26]和MI(OR 1.23;95% CI 1.05 - 1.44)。B等位基因与VT风险增加相关(OR 1.82;95% CI 1.29 - 2.57)和缺血性卒中(OR 1.59;95% CI 1.17 - 2.17)。AB双倍型类别与VT风险增加2.7倍相关(OR 2.70;95% CI 1.73 - 4.21)。没有其他关联达到显著水平。
VT和MI的研究结果具有证实性,B等位基因与缺血性卒中的关联是一项新发现,需要重复验证。