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血小板糖蛋白 Ia 和 IIIa 的多态性与 2 型糖尿病中的动脉血栓形成和颈动脉粥样硬化有关。

Polymorphisms in platelet glycoproteins Ia and IIIa are associated with arterial thrombosis and carotid atherosclerosis in type 2 diabetes.

机构信息

1Endocrinology and Nutrition Service, Department of Internal Medicine, Universitat Autònoma de Barcelona, Germans Trias i Pujol University Hospital, Badalona, Barcelona, Spain.

出版信息

Thromb Haemost. 2010 Mar;103(3):630-7. doi: 10.1160/TH09-07-0453. Epub 2010 Jan 13.

DOI:10.1160/TH09-07-0453
PMID:20076847
Abstract

To determine the genotype distributions of the polymorphisms in platelet glycoproteins (GP) Ib-alpha, Ia/IIa and IIb/IIIa and their association with clinical arterial thrombosis and preclinical carotid atherosclerosis in type 2 diabetes we studied 229 patients with type 2 diabetes and 229 controls matched by age, gender and ethnicity. Biochemical and haemostasis analyses were performed. The GP Ib-alpha VNTR, GP Ia 807 C/T and GP IIIa Pl(A) polymorphisms were determined by PCR. Thrombotic events were registered and carotid atherosclerosis was evaluated by ultrasound examination. A total of 107 patients had clinical atherothrombosis (CA), 65 subclinical atherosclerosis (SA), and 57 had no evidence of atherosclerosis (NA). There were no differences in allele frequencies and the genotype distribution of platelet GP polymorphisms between diabetic patients and controls. The VNTR Ib-alpha polymorphism was not associated with CA. We found a significant association between CA and the 807T (odds ratio [OR]: 2.86, confidence interval [CI]: 1.65-4.93; p<0.001) and PlA2 (OR: 2.03, CI: 1.13-3.65; p=0.03) alleles (in GP Ia and GP IIIa, respectively) in comparison to SA and NA group. Diabetic patients with the coexistence of the 807T and PlA2 alleles presented the highest risk of CA (OR: 3.59, CI: 1.64-7.8; p<0.001). The coexistence of both 807T and PlA2 alleles was also associated with the presence of SA (OR: 9.00, CI: 1.10-73.42; p=0.04). In conclusion, the 807T allele of GP Ia and the PlA2 allele of GP IIIa, and specially its combination, may confer an additional risk for development of carotid atherosclerosis and arterial thrombosis in type 2 diabetes.

摘要

为了确定血小板糖蛋白(GP)Ib-α、Ia/IIa 和 IIb/IIIa 多态性的基因型分布及其与 2 型糖尿病患者临床动脉血栓形成和临床颈动脉粥样硬化的关系,我们研究了 229 例 2 型糖尿病患者和 229 例年龄、性别和种族匹配的对照组。进行了生化和止血分析。通过 PCR 确定了 GP Ib-αVNTR、GP Ia 807C/T 和 GP IIIa Pl(A)多态性。记录血栓事件,并通过超声检查评估颈动脉粥样硬化。共有 107 例患者发生临床动脉血栓形成(CA),65 例发生亚临床动脉粥样硬化(SA),57 例无动脉粥样硬化证据(NA)。糖尿病患者和对照组之间血小板 GP 多态性的等位基因频率和基因型分布无差异。Ib-αVNTR 多态性与 CA 无关。我们发现 CA 与 807T(优势比[OR]:2.86,置信区间[CI]:1.65-4.93;p<0.001)和 PlA2(OR:2.03,CI:1.13-3.65;p=0.03)等位基因(分别在 GP Ia 和 GP IIIa 中)显著相关,与 SA 和 NA 组相比。同时存在 807T 和 PlA2 等位基因的糖尿病患者发生 CA 的风险最高(OR:3.59,CI:1.64-7.8;p<0.001)。807T 和 PlA2 等位基因的共存也与 SA 的存在相关(OR:9.00,CI:1.10-73.42;p=0.04)。总之,GP Ia 的 807T 等位基因和 GP IIIa 的 PlA2 等位基因,特别是它们的组合,可能会增加 2 型糖尿病患者发生颈动脉粥样硬化和动脉血栓形成的风险。

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