Platelet collagen receptor alpha 2 beta 1 integrin and glycoprotein IIIa pl(A1/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 infarct ion, stroke, and diabetic retinopathy. To identify risk factors for their d evelopment in a cohort of patients with type 2 diabetes, we evaluated clini cal variables and genetic polymorphisms in the alpha2 beta1 integrin and GP IIIa genes. Two hundred thirty-four subjects with type 2 diabetes (126 pati ents with and 108 patients without diabetic nephropathy), as well as 217 no ndiabetic healthy subjects, were recruited for this study. Clinical factors for investigation included sex, age at diagnosis, duration of diabetes, bo dy 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 anal yses. No difference in the BgI II polymorphism of the alpha2 beta1 integrin gene was found between patients with type 2 diabetes with or without nephr opathy (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 fo ur independent predictors for the development of diabetic nephropathy. No c ontribution of the BgI II+ allele of the alpha2 beta1 integrin was found fo r the risk for nephropathy (odds ratio, 1.258; 95% confidence interval, 0.6 55 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(1 c) level are strong predictors for nephropathy in patients with type 2 diab etes. However, the BgI II polymorphism of the alpha2 beta1 integrin gene an d the Apa I polymorphism of the platelet GPIIIa gene do not have a major ro le in the development of diabetic nephropathy in our population. (C) 2001 b y the National Kidney Foundation, Inc.