The 5' Insulin Gene Polymorphism and the Genetics of Vascular Complications in Type 1 (insulin-dependent) Diabetes Mellitus

Recent data suggest genetic contributions to the microvascular complications of Type 1 (insulin-dependent) diabetes mellitus. Most research has focused on the HLA region, and the potential role of other genetic loci has not been adequately explored. We examined the possible relationship between DNA polymorphisms in the region 5' to the insulin gene on chromosome 11 and diabetic nephropathy. This was done by comparison of those diabetic patients homozygous for class 1 alleles at the 5' insulin gene polymorphism locus to 1/3 heterozygotes in a well-characterized series of 324 insulin-requiring diabetic patients from the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Proteinuria (defined as greater than or equal to 0.3 g protein/l urine), was used as suggestive evidence for diabetic nephropathy. Hypertension, a frequent associated finding in diabetic patients with nephropathy, was defined as a blood pressure greater than 140/90 or a history of previous treatment of hypertension. The two genotypically defined groups did not differ from each other in regard to sex ratio, age at diagnosis, age at examination, duration of diabetes, body mass, HbAlc or C-peptide. The 1+1 group had a higher prevalence of proteinuria, 29% as compared to 16.2% in other genotypes (p less than 0.05). There was no significant difference in the frequency of hypertension between the two genotypic groups. This finding suggests that the 5' insulin gene polymorphism may be associated with risk for nephropathy, but the pathophysiologic mechanism remains unclear.