Gardemann A, Arsic T, Katz N, Tillmanns H, Hehrlein F W, Haberbosch W
Institut für klinische Chemie und Pathobiochemie, Justus-Liebig-Universität Giessen, Germany.
Thromb Haemost. 1999 Feb;81(2):208-13.
G to A transitions at nucleotide position 20210 of the factor II (Fll) gene and at 1691 of the factor V (FV) gene have been shown to be associated with an increased risk of venous thrombosis. Since it is still unclear whether both gene variations are also related to an increased risk of coronary heart disease (CHD), we studied the relation of both gene variations to coronary artery disease (CAD) and myocardial infarction (MI) in a sample of 2210 male individuals whose coronary anatomy were defined by coronary angiography.
In the total sample, the FII G20210A gene variation was not associated with the presence or the extent of CAD, the latter defined either by the degree of vessel disease or by a CHD score according to Gensini. However, individuals with unfavourable lipid profiles showed pronounced differences in CHD scores between GA heterozygotes and GG homozygotes: this observation applied in particular to younger patients (<62 years; mean age of total sample) who simultaneously had low apoAI/apoB ratios (< 1.19, mean value) and high Lp(a) plasma levels (>28 mg/dl; mean value). In addition, in subjects without acetylsalicylic acid treatment GA heterozygotes had clearly higher CHD scores than AA genotypes. Further restriction to smokers, to subjects with high fibrinogen plasma levels (>3.47 g/l; mean value) or to patients with high glucose concentrations (>112 mg/dl; mean value) tended to increase the difference in CHD score between FII G20210A genotypes. An association of the FII G20210A gene variation with non-fatal MI was not observed. In the total sample and in high and low risk subpopulations, an association of the FV G1691A gene variation was not detected neither with presence and extent of CAD or with nonfatal MI.
The importance of the factor II G20210A gene variation for CHD may be restricted to individuals with major cardiovascular risk factors. In addition, the present study did not strengthen the hypothesis of the factor V G 1691 A transition as a risk factor of coronary heart disease neither in the total sample nor in subgroups of individuals who were at high or low risk of CHD.
已表明凝血因子II（FII）基因核苷酸位置20210处的G到A转换以及凝血因子V（FV）基因1691处的转换与静脉血栓形成风险增加相关。由于目前仍不清楚这两种基因变异是否也与冠心病（CHD）风险增加有关，我们在2210名男性个体样本中研究了这两种基因变异与冠状动脉疾病（CAD）和心肌梗死（MI）的关系，这些个体的冠状动脉解剖结构通过冠状动脉造影确定。
在整个样本中，FII G20210A基因变异与CAD的存在或程度无关，CAD的程度通过血管疾病程度或根据Gensini的冠心病评分来定义。然而，脂质谱不良的个体中，GA杂合子和GG纯合子在冠心病评分上存在显著差异：这一观察结果尤其适用于年龄较小的患者（<62岁；整个样本的平均年龄），他们同时具有较低的载脂蛋白AI/载脂蛋白B比值（<1.19，平均值）和较高的血浆Lp(a)水平（>28mg/dl；平均值）。此外，在未接受乙酰水杨酸治疗的受试者中，GA杂合子的冠心病评分明显高于AA基因型。进一步将研究对象限制为吸烟者、血浆纤维蛋白原水平高（>3.47g/l；平均值）的受试者或血糖浓度高（>112mg/dl；平均值）的患者，FII G20210A基因型之间的冠心病评分差异往往会增大。未观察到FII G202A基因变异与非致命性心肌梗死之间存在关联。在整个样本以及高风险和低风险亚组中，均未检测到FV G1691A基因变异与CAD的存在及程度或非致命性心肌梗死之间存在关联。
凝血因子II G20210A基因变异对冠心病的重要性可能仅限于具有主要心血管危险因素的个体。此外，本研究并未强化凝血因子V G1691A转换作为冠心病危险因素的假设，无论是在整个样本中还是在冠心病高风险或低风险个体亚组中。
