TGF-β1 and IGF-I gene variations in type 1 diabetes microangiopathic complications

Abstract

BackgroundGrowth factors are generally believed to have a perpetuating role in the development of diabetic complications, However there is ample of evidence of a protective or therapeutic potential for some of them. IGF-I, according to some reports, may contribute to complication development, although a protective role for IGF-I has been claimed for all late diabetic complications, making it an exception among growth factors. Transforming growth factor (TGF)-β1 as a pleiotropic cytokine is a key player in immunoregulation. Dysregulation of TGF-β1 in diabetes has been addressed as a leading event of kidney pathologies, while there is no similar pivotal role for TGF-β1 in diabetic retinopathy or neuropathy. An association study was conducted to evaluate the distinctive roles of TGF-β1 and IGF-I in T1DM microvascular complications by gene variation-based regulatory mechanisms that are operational in modulation of both in situ and systemic levels of the gene product.MethodsTwo polymorphisms of the IGF-I gene at positions −383*C/T and −1089*C/T and two functional TGF-β1 gene polymorphisms, including codons 10 (+869*C/T) and 25 (+915*G/C) were examined in 248 British Caucasian T1DM patients and 113 healthy controls.ResultsThe distribution of IGF-1 gene polymorphisms did not reflect any significant association with different endpoints among the cases or different subgroups (complication triad) and controls. For TGF-β1 gene codon 25 polymorphism the low producer variant (allele C) were more frequent in cases than controls, which is compatible with the anti-inflammatory role of TGF-β1 and for codon 10 polymorphism the frequency of allele C was highest in retinopaths and, on the contrary and expectedly, nephropathy was more frequently accompanied by allele T (high producer). The frequency of allele G (high producer) of codon 25 polymorphism was slightly higher in the complication free group than in other subgroups.ConclusionAlthough there were some differences in distribution of allele and genotype frequencies of TGF-β1 gene polymorphism in diabetes microvascular complications the differences were not statistically significant. Regarding IGF-1 our result firstly questions the functionality of the employed polymorphic marker and secondly may entail that the main regulator of IGF-I functionality resides elsewhere rather than the IGF-I gene itself, such as post-transcriptional regulation.

PECAM-1 Leu125Val (rs688) Polymorphism and Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus

“…Similar to our study, Kamiuchi et al were unable to prove an association between PECAM-1 Val125Leu polymorphism and the presence of diabetic retinopathy in subjects with T2DM [20], whereas Bazzaz et al found no correlation between PECAM-1 Val125Leu polymorphism and microangiopathic complications in subjects with type 1 diabetes [35]. In Japanese subjects with T2DM, PECAM-1 Val125Leu polymorphism was not associated with chronic kidney disease [36].…”

Update on genetics and diabetic retinopathy

“… 105 However, a study of 361 British Caucasian patients reported no significant associations between the rs1982073 (T869C) or rs1800471 (R25P) polymorphisms and DR in type 1 diabetes. 106 …”

IGF1gene polymorphisms associated with diabetic retinopathy risk in Chinese Han population

“…In structure, IGF1 is highly homologous with pro-insulin, also including receptor. It is identified to contribute to the main pathways in the progression of DM complications by endocrine [ 12 ]. What's more, IGF1 is reported to be involved in the development of epiretinal membranes (ERMs) which are a layer of pathologic tissues and are very important pathological conditions for DR [ 13 – 15 ].…”