G-protein beta(3) subunit C825T variant, nephropathy and hypertension in patients with type 2 (non-insulin-dependent) diabetes mellitus

Background: There is substantial evidence that hereditary factors contribut e to the predisposition to diabetic nephropathy. On the other hand, it has been suggested that genetics of diabetic nephropathy and hypertension may o verlap. Recently, a C to T substitution (C825T) in the gene encoding for th e guanine-nucleotide-binding protein pg subunit (GNB3) was identified, and this molecular variant was found to be associated with enhanced activation of G proteins and increased risk of the development of hypertension. The ai m of the study was to test whether GNB3 C825T polymorphism contributes to t he development of incipient or overt nephropathy or hypertension in type 2 diabetic patients. Methods: GNB3 genotype was determined in 130 type 2 diab etic patients with overt proteinuria or chronic renal failure, 155 diabetic patients with microalbuminuria and 163 control subjects with normoalbuminu ria and known type 2 diabetes duration of at least 10 years. Results: No di fferences in GNB3 genotype distributions or allele frequencies between the study groups were found. Also, no differences between normotensive and hype rtensive patients were demonstrated. Conclusion: The study provided evidenc e against the major impact of the GNB3 C825T polymorphism on the increased risk of the development of nephropathy or hypertension in type 2 diabetic p atients. Copyright (C) 2000 S. Karger AG. Basel.