ACE gene polymorphism and diabetic complications: is there a connection?

The insertion/deletion (I/D) polymorphism of the ACE gene accounts for 50% of the variation in serum ACE levels and activity. However, its functional significance with regard to diabetic complications and cardiovascular disease remains controversial. To review the literature assessing the significance of ACE gene polymorphism on the initiation and progression of diabetic complications and treatment implications, a systematic review of the Medline, Pubmed and EMBASE databases was performed. Keywords were 'diabetes mellitus', 'diabetic nephropathy', 'ACE gene polymorphism' and 'genotype', for the period 1966 to August 1999. Overall, ACE gene polymorphism appears to affect the progression of diabetic nephropathy, with individuals homozygous for the deletion allele (DD) having a shorter time period from the onset of microalbuminuria to renal replacement therapy and decreased survival thereafter. This may reflect relative resistance to ACE inhibitor therapy. There is no association between ACE gene polymorphism and retinopathy. Further large prospective studies are required to clarify the association of ACE gene polymorphism and diabetic complications. However, it appears that the deletion allele acts in a co-dominant manner as a susceptibility factor in the progression of diabetic nephropathy. ACE genotyping may therefore provide a simple method of identifying high risk individuals and allow the implementation of early and aggressive therapy.