de Maat M P, Bladbjerg E M, Johansen L G, de Knijff P, Gram J, Kluft C, Jespersen J
Department of Thrombosis Research, University of Southern Denmark, Ribe County Hospital, Esbjerg.
Thromb Haemost. 1999 Apr;81(4):547-52.
Greenland Inuit are a population with a low risk of cardiovascular disease. Recently, we stated that frequencies of potentially high risk alleles of the apolipoproteins, fibrinogen, factor V, glycoprotein IIIa and factor VII (FVII) genes have different allele frequencies in the Inuit when compared with Caucasian populations. We have extended this study and evaluated whether or not this was also true for the genetic polymorphisms of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), angiotensin-converting enzyme (ACE) and angiotensinogen in a group of 133 Greenland Inuit, aged 30-34 gamma. In addition, we compared the plasma levels of these factors and those of C-reactive protein (CRP) and D-Dimer in Inuit and in Danes, comparable for age and gender. Frequencies (f) were assessed of the alleles that are known as the potential high risk alleles in Caucasians. In the Inuit, the f(insertion allele) of the t-PA intron8ins311 polymorphism was 0.37 (CI 0.32-0.43), the f(4G allele) of the PAI-1 promoter polymorphism was 0.88 (CI 0.83-0.91), the f(deletion allele) of the ACE intron16ins287 polymorphism was 0.40 (CI 0.33-0.47) and the f(M-allele) of the angiotensinogen M/T353 polymorphism was 0.30(CI 0.25-0.38). As for fibrinogen and FVII polymorphisms, these frequencies are all significantly different from what is reported for Caucasian populations. In the Inuit, plasma levels of fibrinogen and D-Dimer were higher than in the Danes, the PAI-1 levels were lower and FVII, t-PA and CRP levels were comparable. The observed allele frequencies of the polymorphisms of t-PA, fibrinogen, FVII, ACE, angiotensinogen and the plasma levels of PAI-1 and D-Dimer were in accordance with the low CVD risk in the Inuit, considering the observed associations between these measures and CVD risk in Caucasian populations, but for other measures this was not the case (allele frequencies of the PAI-1 polymorphism, and plasma levels of fibrinogen, FVII and t-PA). In conclusion there are clear differences in genetic background and plasma levels of risk factors in Greenland Inuit compared with Caucasian populations, and these differences were sometimes, but not always, in accordance with the observed low cardiovascular disease risk of the Inuit population.
格陵兰因纽特人患心血管疾病的风险较低。最近，我们指出，与白种人群相比，载脂蛋白、纤维蛋白原、凝血因子V、糖蛋白IIIa和凝血因子VII（FVII）基因潜在高风险等位基因的频率在因纽特人中有所不同。我们扩展了这项研究，评估了组织型纤溶酶原激活剂（t-PA）、纤溶酶原激活剂抑制剂-1（PAI-1）、血管紧张素转换酶（ACE）和血管紧张素原的基因多态性在133名年龄在30 - 34岁的格陵兰因纽特人中是否也是如此。此外，我们比较了因纽特人和丹麦人（年龄和性别匹配）这些因子以及C反应蛋白（CRP）和D-二聚体的血浆水平。评估了白种人中已知的潜在高风险等位基因的频率。在因纽特人中，t-PA内含子8插入311多态性的f（插入等位基因）为0.37（95%置信区间0.32 - 0.43），PAI-1启动子多态性的f（4G等位基因）为0.88（95%置信区间0.83 - 0.91），ACE内含子16插入287多态性的f（缺失等位基因）为0.40（95%置信区间0.33 - 0.47），血管紧张素原M/T353多态性的f（M等位基因）为0.30（95%置信区间0.25 - 0.38）。至于纤维蛋白原和FVII多态性，这些频率与白种人群的报道均有显著差异。在因纽特人中，纤维蛋白原和D-二聚体的血浆水平高于丹麦人，PAI-1水平较低，FVII、t-PA和CRP水平相当。考虑到在白种人群中观察到的这些指标与心血管疾病风险之间的关联，t-PA、纤维蛋白原、FVII、ACE、血管紧张素原多态性的观察等位基因频率以及PAI-1和D-二聚体的血浆水平与因纽特人低心血管疾病风险一致，但对于其他指标并非如此（PAI-1多态性的等位基因频率以及纤维蛋白原、FVII和t-PA的血浆水平）。总之，与白种人群相比，格陵兰因纽特人的遗传背景和风险因子血浆水平存在明显差异，这些差异有时但并非总是与因纽特人群中观察到的低心血管疾病风险一致。
