MOLECULAR METHODS FOR THE STUDY OF THE GENETIC-DETERMINANTS OF NEPHROPATHY IN TYPE-1 (INSULIN-DEPENDENT) DIABETES

Recently, evidence has accumulated that genetic factors may contribute to the development of diabetic nephropathy in patients with type 1 (i nsulin-dependent) diabetes mellitus. To identify variation at a gene l ocus, newly developed methods are introduced which employ denaturing g radient gel electrophoresis (DGGE) to study sequence differences in po lymerase chain reaction (PCR)-amplified DNA fragments as well as in ge nomic DNA. These techniques are illustrated with studies of the angiot ensinogen gene and the insulin receptor gene. In preliminary data from a comparison between individuals with and without diabetic nephropath y, we found no DNA sequence difference in the part of the angiotensino gen gene coding for angiotensin I. We did find, however, different dis tributions of a DNA polymorphism detected with the probe corresponding to exons 7 and 8 of the insulin receptor gene in RsaI DGGE blots in a comparison of patients with slow and fast progressing nephropathy. Th e interpretation of this finding and the need for further studies are discussed. In conclusion, the advent of methods of molecular genetics makes possible studies on genetic determinants of diabetic nephropathy . However, more clinical and epidemiological data are needed to find o ut how many genes are involved and how they interact with exposure to diabetes. Foremost, DNA from families with two or more siblings with d iabetic nephropathy must be collected so that genetic studies will be possible.