HAPTOGLOBIN POLYMORPHISM AS AN INDEPENDENT PREDICTOR OF DIABETIC NEPHROPATHY AND RETINOPATHY

INTRODUCTION: The antioxidant protein haptoglobin (Hp) plays a major role in the development of diabetic complications such as diabetic nephropathy and retinopathy. In humans, two alleles of Hp were identified: 1 and 2 with three possible genotypes: 1-1, 2-1, and 2-2. The Hp protein products differ in their biochemical and biophysical properties, such as their antioxidant capacity. The Hp1 protein is superior to the Hp2 protein in binding to free hemoglobin and neutralizing its oxidative potential and the accompanying renal and retinal injury. Hence, diabetic patients with different Hp phenotypes have variable susceptibility to developing diabetic nephropathy and retinopathy. In diabetes, the kidney and the retinal injury progress gradually over time. Thus, understanding the factors that mediate the aggravation and progression of these complications is of critical importance. One of the latest hypotheses regarding the involvement of haptoglobin in the development of diabetic complications is its contribution to impaired vitamin D activation in the kidney. Over the last few years, great efforts were made in the field to explore this notion and decrypt the mechanism behind it. The goal in this area is that the research findings will be translated into clinical practice and lead to the development of a pharmacogenomics clinical approach that will deal with diabetic complications by selective administration of vitamin D according to the Hp genotype.