纤维蛋白原βG-455A基因多态性与血浆纤维蛋白原及冠心病的关系

Association of fibrinogen βG-455A polymorphism with plasma fibrinogen level in patients with coronary heart disease

目的研究中国人群中纤维蛋白原βG-455A基因多态性与血浆纤维蛋白原水平及冠心病亚型的关系。方法1 485例因胸痛或非侵入性检查提示心肌缺血的成年人进行了冠状动脉造影检查,根据临床表现及冠状动脉造影结果被分为冠心病组(n=1 019)及对照组(n=466),冠心病组又被分为稳定型心绞痛(SAP)组(n=674)及急性冠状动脉综合征(ACS)组(n=345)。应用vonClauss法测定血浆纤维蛋白原水平,多聚酶链反应(PCR)和HaeⅢ内切酶技术检测纤维蛋白原βG-455A基因多态性。结果ACS组及SAP组的血浆纤维蛋白原水平较对照组显著升高,其中ACS组最高(ACS组380.92±92.35 mg/dL,SAP组352.49±94.89 mg/dL,对照组311.72±87.09 mg/dL,三组之间两两比较,P均<0.001)。在对照组及SAP组中基因型为AA的纯合子其血浆纤维蛋白原水平较携带G等位基因的个体为高(对照组AA为363.83±76.66 mg/dL,与GA的337.83±77.43mg/dL或GG的295.28±88.06 mg/dL比较,P均<0.05;SAP组AA为429.82±93.35 mg/dL,与GA的368.30±90.39 mg/dL或GG的337.89±94.32 mg/dL比较,P均<0.05),而在ACS组未见此趋势。各组之间的基因型及等位基因频率分布差异无统计学意义(P>0.05),-455A等位基因与冠心病发病风险无相关性。结论血浆纤维蛋白原水平升高与冠心病发病风险相关。纤维蛋白原βG-455A基因多态性与冠心病发病无相关性。

Objective To evaluate whether βG-455A gene polymorphism increases the risk of coronary heart disease （CHD） due to elevated plasma fibrinogen. Methods A total of 1 485 patients who had received coronary angiography due to chest pain or suspected cardiac ischemia by non-invasive examination were included in the study. According to the angiographic results, all the patients were divided into the control group （n =466） and coronary heart disease group （n = 1 019）. Patients in the coronary heart disease group were further divided into stable angina pectoris group （ SAP, n = 674 ） and acute coronary syndrome group （ACS, n = 345） according to their clinical presentation. We investigated G-455A polymorphism of β fibrinogen gene and plasma fibrinogen level in all the patients. Results Increased plasma fibrinogen levels were observed in CHD groups compared with controls （ACS. 380.92 ± 92. 35 mg/dL, SAP： 352. 49 ± 94. 89 mg/dL, control ： 311.72 ± 87.09 mg/dL, P 〈 0. 001 ）. Individuals with the -455AA genotype were associated with the highest plasma fibrinogen in controls （ AA： 363.83 ± 76. 66 mg/dL,GA： 337.83 ±77.43 mg/dL, GG： 295.28 ±88.06 mg/dL, P 〈0.001） and SAP group （AA： 429. 82 ±93.35 mg/dL, GA： 368.30 ±90. 39 mg/dL, GG： 337.89 ±94. 32 mg/dL, P 〈0. 001 ）, but not in ACS group. Gene frequency and genotype distribution were similar among the three groups （P = 0. 314）. Conclusion Elevated plasma fibrinogen level is related to increased CHD risk. The presence of -455Aallele is tightly associated with higher fibrinogen in normal and SAP individuals but not ACS, and βG-455A polymorphism is not associated with CHD.