The Role of Haptoglobin Polymorphism in Gene Expression of CD163 Receptors in Obesity

Abstract

Haptoglobin (Hp) is a polymorphic plasma protein existing in three phenotypes: Hp 1-1, Hp 2-1, and Hp 2-2. The best-known function of Hp is binding with free hemoglobin (Hb) in circulation preventing loss of iron and kidney damage. In circulation, free Hb is a potent redox-active compound that can participate in the Fenton reactions inducing the formation of reactice oxygen species (ROS) causing tissue damage. Free Hb, however, is immediately captured by haptoglobin forming a stable hemoglobin-haptoglobin (Hb-Hp) complex that is rapidly cleared from circulation by biding with CD163 receptors on the surface of macrophage and monocytes. Along with CD163, the Hb-Hp complexes are internalized by endocytosis and the heme subunit of hemoglobin is degraded by heme-oxygenase (HO-1) into biliverdin, free iron and carbon monoxide. Previous studies have demonstrated that handling of heme-iron and the antioxidative protection conferred by Hp is phenotype-dependent. Hp 2-2 phenotype is an inferior antioxidant as compared with Hp 1-1 or Hp 2-1. Individuals with Hp 2-2 phenotype are under greater oxidative stress (OS) as evidenced by decreased clearance rate of free Hb and increased levels of oxidized LDL-cholesterol.