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.