Platelet collagen receptor α2β1 integrin and glycoprotein IIIa plA1/A2 polymorphisms are not associated with nephropathy in Type 2 diabetes

Platelet glycoprotein receptors play a role in the pathogenesis of chronic diabetic complications. Genetic polymorphisms of the alpha2 beta1 integrin and glycoprotein IIIa (GPIIIa) have been associated with myocardial infarction, stroke, and diabetic retinopathy. To identify risk factors for their development in a cohort of patients with type 2 diabetes, we evaluated clinical variables and genetic polymorphisms in the alpha2 beta1 integrin and GPIIIa genes. Two hundred thirty-four subjects with type 2 diabetes (126 patients with and 108 patients without diabetic nephropathy), as well as 217 nondiabetic healthy subjects, were recruited for this study. Clinical factors for investigation included sex, age at diagnosis, duration of diabetes, body mass index (BMI), and fasting plasma glucose, hemoglobin A(1c) (HbA(1c)), total cholesterol, and triglyceride levels. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analyses. No difference in the BgI II polymorphism of the alpha2 beta1 integrin gene was found between patients with type 2 diabetes with or without nephropathy (11 [8.7%], 47 [37.3%], and 68 patients [54.0%] versus 10 [9.3%], 32 [29.6%], and 66 patients [61.1%] for BgI II+/+, BgI II+/-, and BgI II-/-, respectively; P = 0.271). Multiple logistic regression analyses showed that duration of diabetes, BMI, hypertension, and poor glycemic control were four independent predictors for the development of diabetic nephropathy. No contribution of the BgI II+ allele of the alpha2 beta1 integrin was found for the risk for nephropathy (odds ratio, 1.258; 95% confidence interval, 0.655 to 2.418; P = 0.490). The pI(A2) allele genotype was not found among our studied subjects. In conclusion, age, duration of diabetes, BMI, and HbA(1c) level are strong predictors for nephropathy in patients with type 2 diabetes. However, the BgI II polymorphism of the alpha2 beta1 integrin gene and the Apa I polymorphism of the platelet GPIIIa gene do not have a major role in the development of diabetic nephropathy in our population. (C) 2001 by the National Kidney Foundation, Inc.