Genetics of diabetic neuropathy: study of VEGF gene

ABSTRACT

Vascular factors in conjunction with metabolic issues are involved in both etiopathogenesis of diabetic neuropathy [DNU], and more remarkably in [repair] phase, when the net balance between neuroregenerative/degenerative reactions is dictated to some extent by these factors. The ischemic nature of DNU indicates the importance of re-establishment of blood vessels. VEGF, a growth factor which, in addition to its hemodynamic effects, possesses an [angiogenic] capacity has been the subject of extensive investigations in DNU, especially, interventional therapies. The impacts of racial and inherited backgrounds in the development of DNU suggest that the genetic issues partially govern the outcome of diabetic late complications, including DNU. By conducting a candidate gene case-control association study, present study explores the possibility if the inter-individual variations of VEGF gene structure by any means encode the genetic susceptibility/resistance in the course of DNU. The distribution of VEGF gene polymorphisms frequencies were analyzed at positions -7[*]C/T, -1001 [*]G/C, -1154[*]G/A and -2578[*]C/A and were evaluated by ARMS-PCR in 248 type 1 diabetic subjects [81 DNU[+], 167 DNU[-] and 113 healthy controls, all from [British-Caucasian] origin. When the frequency of the polymorphic alleles/genotypes between patients and controls, and also between two subgroups within patients' group with each other [DNU[+] vs. DNU[-]] or with healthy controls were compared, only in one situation a significant difference was evident. The distribution of a VEGF gene polymorphism at promoter region [-7[*]C/T] at allelic [but not at genotypic] level was notably different between diabetics, with and without neuropathy, while the minor allele [T] conferred a protective effect [P=0.03; OR = 1.75]. The present study may imply a prognostic value for VEGF gene polymorphism at promoter region [-7[*]C/T] in DNU. However, it requires further studies to appreciate better the phenotypic impact of this polymorphism in this chronic complication of diabetes. A catalog of candidate genes polymorphisms that functionally reflect a protection/predisposition to DNU can provide the genotypic profile that can be useful to reasonably predict the overall behavior of diabetic subjects to the metabolic derangements relative to development of DNU, which in turn may require adoption of relevant preventive and therapeutic measures: