Haptoglobin: A major susceptibility gene for diabetic vascular complications.

Late complications of diabetes mellitus (DM) are the leading cause of adult blindness and end-stage renal disease in the western world, and a major contributor to cardiovascular, cerebrovascular and peripheral vascular disease. The etiology of the development of chronic complications of DM is unclear, and several theories have been proposed to explain the mechanisms involved. Interest in the role of genetic factors predisposing individuals to the vascular complications of DM has grown enormously in recent years. The authors recently published evidence that haptoglobin phenotype may serve as a predictor of the relative risk of diabetes-related vascular disorders. Several mechanisms whereby haptoglobin phenotype may determine diabetic vascular complications are presented. First, the haptoglobin protein products of the different alleles differ in their antioxidant capacity. Second, the haptoglobin polymers present in individuals with 1-1, 2-1 or 2-2 phenotype appear to have differential sieving properties. Third, the haptoglobin types appear to differ in their immunomodulatory functions. These studies point towards haptoglobin phenotype as a new risk factor for vascular disease in diabetes. In addition to providing insight into the pathogenesis of diabetic vascular complications, these studies suggest a new therapeutic target for prevention of these diseases.