Genetics of diabetic nephropathy

Diabetic nephropathy can develop in up to one-third of patients with type 1 diabetes and approximately 25% of patients with type 2 diabetes. This complication is important as it not only leads to renal failure but is associated with a high risk of coronary artery disease and other vascular complications. Although hyperglycaemia is necessary for the development of diabetic nephropathy, it is not sufficient, genetic factors also being important. This is evidenced by studies showing that only a subgroup of patients are at risk of nephropathy and that nephropathy clusters in families. The genes involved in susceptibility to diabetic nephropathy have yet to be identified. Most studies to date have been case–control in design, and there have been conflicting results. Genes suggested as having a role include those encoding angiotensin-1 converting enzyme, apolipoprotein E, heparan sulphate and aldose reductase. In order to clarify the role of these and other candidate genes in nephropathy, association studies in families are necessary. Because of the large number required, this will require international collaboration. A genetic marker for nephropathy would enable the earlier detection of this complication, thus facilitating screening and targeted intervention. An understanding of the role of susceptibility genes will ultimately allow the development of novel therapeutic strategies.