Nagi D K, McCormack L J, Mohamed-Ali V, Yudkin J S, Knowler W C, Grant P J
National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, USA.
Diabetes Care. 1997 Aug;20(8):1304-9. doi: 10.2337/diacare.20.8.1304.
To examine the relationship between plasma plasminogen activator inhibitor 1 (PAI-1) activity and PAI-1 gene (4G/5G) polymorphism and diabetic retinopathy in Pima Indians with type 2 diabetes.
We studied 171 Pima Indians with type 2 diabetes between the ages of 30-70 years in a population-based epidemiological survey. Plasma PAI-1 activity was measured by a spectrophotometric assay and PAI-1 4G/5G promoter genotype by the polymerase chain reaction (PCR) using allele-specific primers. Retinopathy was assessed by ophthalmoscopy after pupillary dilation and classified as any retinopathy or as nonproliferative and proliferative.
Retinopathy was present in 70 (41%) subjects, and 4 (2.3%) subjects had proliferative retinopathy. Plasma PAI-1 activity was not significantly different among subjects with and without retinopathy (17.1 +/- vs. 19.7 +/- 9.1 arbitrary units (AU)/ml, P = 0.09). PAI-1 activity was negatively correlated with duration of diabetes (rs = -0.18, P = 0.02). In a logistic regression analysis controlled for age, sex, BMI, and duration of diabetes, any retinopathy was significantly associated with fasting plasma glucose concentrations (P < 0.05), 2-h postload glucose (P = 0.02), and HbA1c (P = 0.008), but not with PAI-1 activity (P = 0.48). The prevalence of retinopathy in the three genotype groups differed significantly (4G/4G, 4G/5G, and 5G/5G were 44, 49, and 24%, respectively; chi 2 = 8.22, df = 2, P = 0.016) and remained significant after controlling for age, sex, BMI, duration of diabetes, glycated hemoglobin, and urine albumin-to-creatine ratio in a logistic regression analysis. The odds ratios for retinopathy in subjects with 4G/4G and 4G/5G, compared with the 5G/5G genotype, were 2.0 and 3.1, respectively.
Although diabetic retinopathy in Pima Indians with type 2 diabetes is not associated with PAI-1 activity, subjects with the 4G/4G and 4G/5G genotype had a higher prevalence of retinopathy compared with 5G/5G PAI-1genotype. These preliminary findings indicate that in Pima Indians with type 2 diabetes, presence of the 4G allele of the PAI-1 gene was associated with a higher risk of diabetic retinopathy.
研究皮马族2型糖尿病印第安人中血浆纤溶酶原激活物抑制剂1（PAI-1）活性及PAI-1基因（4G/5G）多态性与糖尿病视网膜病变之间的关系。
在一项基于人群的流行病学调查中，我们研究了171名年龄在30至70岁之间的皮马族2型糖尿病印第安人。采用分光光度法测定血浆PAI-1活性，使用等位基因特异性引物通过聚合酶链反应（PCR）检测PAI-1 4G/5G启动子基因型。散瞳后通过检眼镜检查评估视网膜病变，并将其分类为任何视网膜病变、非增殖性视网膜病变和增殖性视网膜病变。
70名（41%）受试者存在视网膜病变，4名（2.3%）受试者患有增殖性视网膜病变。有视网膜病变和无视网膜病变的受试者之间血浆PAI-1活性无显著差异（分别为17.1±和19.7±9.1任意单位（AU）/ml，P = 0.09）。PAI-1活性与糖尿病病程呈负相关（rs = -0.18，P = 0.02）。在一项对年龄、性别、体重指数和糖尿病病程进行校正的逻辑回归分析中，任何视网膜病变均与空腹血糖浓度（P < 0.05）、餐后2小时血糖（P = 0.02）和糖化血红蛋白（P = 0.008）显著相关，但与PAI-1活性无关（P = 0.48）。三个基因型组的视网膜病变患病率差异显著（4G/4G、4G/5G和5G/5G分别为44%、49%和24%；χ2 = 8.22，自由度 = 2，P = 0.016），在对年龄、性别、体重指数、糖尿病病程、糖化血红蛋白和尿白蛋白与肌酐比值进行校正的逻辑回归分析后，差异仍显著。与5G/5G基因型相比，4G/4G和4G/5G基因型受试者发生视网膜病变的比值比分别为2.0和3.1。
虽然皮马族2型糖尿病印第安人中的糖尿病视网膜病变与PAI-1活性无关，但与5G/5G PAI-1基因型相比，4G/4G和4G/5G基因型受试者的视网膜病变患病率更高。这些初步研究结果表明，在皮马族2型糖尿病印第安人中，PAI-1基因4G等位基因的存在与糖尿病视网膜病变的较高风险相关。
