Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
J Thromb Thrombolysis. 2012 Aug;34(2):276-82. doi: 10.1007/s11239-012-0734-6.
The aim of this study was to evaluate the association of prothrombotic gene polymorphisms [factor V Leiden (FVL) 1691GA, factor VII (FVII) 10976GA, FVII HVR4, platelet membrane glycoproteins GP1BA 1018CT, GP1BA VNTR, integrin ITGB3 1565TC, integrin ITGA2 807CT and methylenetetrahydrofolate reductase (MTHFR) 677C/T], plasma factors (fibrinogen and homocysteine) and traditional risk factors with acute myocardial infarction (AMI) in 184 patients ≤ 40 years of age and 350 controls (≤ 40 years) from north India. Multiple logistic-regression analysis showed that hypertension (OR 1.9, 95 % CI 1.1-3.8, p = 0.042), diabetes mellitus (OR 10.5, 95 % CI 2.0-56.7, p = 0.006), smoking (OR 7.1, 95 % CI 3.7-13.6, p < 0.001), low socio-economic status (OR 13.5, 95 % CI 2.3-78.4, p = 0.004), high waist-hip ratio (OR 35.6, 95 % CI 11.1-53.7, p < 0.001) and FVL 1691GA (OR 6.0, 95 % CI 1.2-13.4, p = 0.03) were independent risk predictors of AMI in young. Elevated plasma fibrinogen also showed association with increased AMI risk. ITGA2 807C/T polymorphism showed protection against AMI in univariate analysis only, while GP1BA VNTR-ac (OR 0.4, 95 % CI 0.2-0.9, p = 0.033) showed significant protection even after adjusting for age and sex. Multinominal logistic-regression analysis showed gene-gene (GP1BA 1018C/T with GP1BA VNTR and ITGA2 807C/T with ITGB3 1565T/C polymorphisms) and gene-environment interactions (gene polymorphisms with smoking) operating in the occurrence of AMI in young. In conclusion, the role of inherited predisposition to thrombosis in complex, polygenic and multifactorial disease like AMI is limited to certain genetic factors, in combination with environmental factor like smoking.
本研究旨在评估促血栓形成基因多态性(因子 V 莱顿突变 [FVL] 1691GA、因子 VII [FVII] 10976GA、FVII HVR4、血小板膜糖蛋白 GP1BA 1018CT、GP1BA 长度多态性、整合素 ITGB3 1565TC、整合素 ITGA2 807CT 和亚甲基四氢叶酸还原酶 [MTHFR] 677C/T)、血浆因子(纤维蛋白原和同型半胱氨酸)和传统危险因素与来自印度北部的 184 名≤40 岁的急性心肌梗死(AMI)患者和 350 名对照者(≤40 岁)之间的关系。多因素逻辑回归分析显示,高血压(OR 1.9,95%CI 1.1-3.8,p=0.042)、糖尿病(OR 10.5,95%CI 2.0-56.7,p=0.006)、吸烟(OR 7.1,95%CI 3.7-13.6,p<0.001)、社会经济地位低(OR 13.5,95%CI 2.3-78.4,p=0.004)、高腰臀比(OR 35.6,95%CI 11.1-53.7,p<0.001)和 FVL 1691GA(OR 6.0,95%CI 1.2-13.4,p=0.03)是年轻人 AMI 的独立危险因素。血浆纤维蛋白原升高也与 AMI 风险增加相关。ITGA2 807C/T 多态性仅在单因素分析中显示出对 AMI 的保护作用,而 GP1BA VNTR-ac(OR 0.4,95%CI 0.2-0.9,p=0.033)在调整年龄和性别后仍具有显著的保护作用。多变量逻辑回归分析显示,基因-基因(GP1BA 1018C/T 与 GP1BA VNTR 和 ITGA2 807C/T 与 ITGB3 1565T/C 多态性)和基因-环境相互作用(基因多态性与吸烟)在年轻人 AMI 的发生中起作用。总之,遗传易栓倾向在 AMI 等复杂的多基因和多因素疾病中的作用仅限于某些遗传因素,并与吸烟等环境因素相结合。