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Item #14 

Diabetic Nephropathy May Have Genetic Origins

Certain genes may be associated with the pathogenesis of diabetic nephropathy.

Researchers at the University of Plymouth, England, investigated whether certain genes in the region of the vascular endothelial growth factor gene was associated with susceptibility to diabetic microvascular complications. They pointed to growing evidence which implicated genetic factors in this susceptibility.

Recent studies had suggested that increased expression of cytokine vascular endothelial growth factor might affect the pathogenesis of diabetic complications. Several polymorphisms in the promoter region of the vascular endothelial growth factor gene had been identified, the researchers added.

Two hundred and thirty two patients with type 1 diabetes mellitus and 141 normal healthy controls were studied.

The deletion/deletion genotype was significantly greater in 102 patients with nephropathy than in 66 patients with no complications after 20 years of diabetes.

The combination of polymorphisms of vascular endothelial growth factor plus the aldose reductase gene showed that 8 of 83 patients with nephropathy had the vascular endothelial growth factor I allele together with the Z+2 5'ALR2 allele, compared with 27 of 62 uncomplicated patients.

The functional role of the deletion/insertion polymorphism was investigated through cloning the region into a luciferase reporter assay system and by transient transfection into HepG2 cells.

The construct containing the 18 base pair deletion had a near doubled increase in transcriptional activity compared with its counterpart that had the insert.
Journal of Diabetes and its Complications 2003;17(1):1-6