TGF-beta1 and TSC-22 gene polymorphisms and susceptibility to microvascular complications in type 2 diabetes.

Background/aim: There is a strong evidence for the involvement of genetic factors in diabetic microvascular complications. The aim of our study was to investigate the role of molecular variants of the TGF-beta1 (transforming growth factor beta 1) and the TSC-22 (transforming growth factor beta stimulated clone 22) genes in diabetic nephropathy and diabetic retinopathy in type 2 diabetes.

Methods: A case-control study was conducted in 503 patients and 400 healthy subjects. DNA samples were genotyped by polymerase chain reaction and restriction fragment length polymorphism methods.

Results: Among the patients, 245 had diabetic nephropathy, 195 had retinopathy, and 168 were free from complications. All subjects were genotyped for T869C and C -509T polymorphisms of the TGF-beta1 gene and for -396 polymorphism of the TSC-22 gene. A significantly increased frequency of the CC genotype of the T869C polymorphism was observed in patients with nephropathy and retinopathy (33 and 48%, respectively, vs. 19 and 15%, respectively, in controls and patients free from complications). The frequency of the C allele was also higher (0.58 for nephropathy and 0.64 for retinopathy vs. 0.42 in controls). The G allele of the TSC-22 polymorphism was associated with an increased risk of diabetic nephropathy (frequency 0.15 vs. 0.07 and 0.06, respectively, in patients free from complications and controls). An interaction was observed between the G allele of the TSC-22 polymorphism and the C-allele of the TGF-beta polymorphism.

Conclusions: Our data suggest the association of TGF-beta T869C gene polymorphism with an increased risk of nephropathy and retinopathy in type 2 diabetes patients. It interacts with the TSC-22 gene involved in the TGF-beta signaling pathway, promoting the development of diabetic nephropathy.