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

Journal of Diabetes & Metabolic Disorders

Ian V Hutchinson¹  Vera Pravica¹  Bagher Larijani³  Zahra Taheri³  Mahsa M Amoli³  Javad Tavakkoly Bazzaz² 

[1] School of Pharmacy, University of Southern California (USC), Los Angeles, USA;Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;Endocrinology and Metabolism Research Centre, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran

关键词: Polymorphism;    TGF-β1;    IGF-I;    T1DM;   

Others  :  803624
DOI  :  10.1186/2251-6581-13-45

 received in 2012-09-25, accepted in 2014-03-11,  发布年份 2014

【 摘 要 】

Background

Growth 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.

Methods

Two 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.

Results

The 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.

Conclusion

Although 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.

【 授权许可】

   
2014 Bazzaz et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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