McCormack L J, Nagi D K, Stickland M H, Mansfield M W, Mohamed-Ali V, Yudkin J S, Knowler W C, Grant P J
Unit of Molecular Vascular Medicine, Research School of Medicine, University of Leeds, UK.
Diabetologia. 1996 Dec;39(12):1512-8. doi: 10.1007/s001250050606.
Elevated plasminogen activator inhibitor-1 may contribute to vascular disease in diabetes mellitus. Pima Indians have a low incidence of cardiovascular disease despite having a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM) which in this population is not associated with elevated plasminogen activator inhibitor-1 activity. In Caucasians an insertion/deletion (4G/5G) polymorphism in the promoter region of the plasminogen activator inhibitor-1 gene that has been related to activity levels of its protein in plasma differentially binds repressor and enhancer elements. In 265 Pima Indians (133 diabetic, 132 non-diabetic, 129 male, 136 female, male, mean age 46.6, range 34-68 years) the promoter genotype frequencies were 23.0% for 4G/4G, 49.8% for 4G/5G and 27.2% for 5G/5G compared to 35.4%, 50.8% and 13.8% respectively, (chi 2 = 15.3, 2 df, p < 0.0005) previously reported in Caucasians with NIDDM. The mean plasma activity levels in the three genotypes in the Pima Indians were 18.2, 19.1 and 18.1 U/ml, respectively. Plasminogen activator inhibitor-1 activities correlated with plasma insulin (r = 0.38, p < 0.0001), body mass index (r = 0.24, p < 0.0001), and with triglyceride level (r = 0.12, p = 0.054) but there was no relationship between promotor genotype and activity. A steeper regression slope between plasminogen activator inhibitor-1 activity and triglycerides has been observed in Caucasians with the 4G/4G genotype as compared to Caucasians with the other genotypes. This was not found in the Pima population which may indicate a functional difference in this gene associated with reduced cardiovascular risk and may be involved in the lack of association of plasminogen activator inhibitor-1 levels with NIDDM in Pima Indians.
纤溶酶原激活物抑制剂-1升高可能与糖尿病血管疾病有关。皮马印第安人尽管非胰岛素依赖型糖尿病（NIDDM）患病率很高，但心血管疾病发病率较低，在该人群中，NIDDM与纤溶酶原激活物抑制剂-1活性升高无关。在白种人中，纤溶酶原激活物抑制剂-1基因启动子区域的插入/缺失（4G/5G）多态性与血浆中其蛋白质的活性水平相关，该多态性可差异结合阻遏元件和增强子元件。在265名皮马印第安人（133名糖尿病患者、132名非糖尿病患者、129名男性、136名女性，男性平均年龄46.6岁，年龄范围34 - 68岁）中，4G/4G启动子基因型频率为23.0%，4G/5G为49.8%，5G/5G为27.2%，而之前报道的患有NIDDM的白种人相应频率分别为35.4%、50.8%和13.8%，（卡方检验=15.3，自由度为2，p<0.0005）。皮马印第安人三种基因型的平均血浆活性水平分别为18.2、19.1和18.1 U/ml。纤溶酶原激活物抑制剂-1活性与血浆胰岛素（r = 0.38，p<0.0001）、体重指数（r = 0.24，p<0.0001）以及甘油三酯水平（r = 0.12，p = 0.054）相关，但启动子基因型与活性之间无关联。与其他基因型的白种人相比，4G/4G基因型的白种人纤溶酶原激活物抑制剂-1活性与甘油三酯之间的回归斜率更陡。在皮马人群中未发现这种情况，这可能表明该基因存在功能差异，与心血管风险降低相关，并且可能与皮马印第安人纤溶酶原激活物抑制剂-1水平与NIDDM缺乏关联有关。
