Unique Assembly Structure Of Human Haptoglobin Phenotypes 1-1, 2-1, And 2-2 And A Predominant Hp1 Allele Hypothesis

Abstract

Human plasma haptoglobin (Hp) is classified as three phenotypes, Hp 1-1, 2-1 and 2-2. They are attributed by Hp 1 and Hp 2 alleles with each producing a α1β and α2β polypeptide chain, respectively. Owing to the various content of -SH groups in each peptide, the heterogeneous and polymeric structural arrangement via the disulfide linkages is totally different among the phenotypes. The resulting molecular size of Hp 2-2 [(α2β)n] and 2-1 [(α1β)2 (α2β)n] is dramatically larger than that of 1-1 [(α1β)2]. In the present study, we observed that there were as many as 20 repeated units in Hp 2-2 as compared that only 10 repeats in Hp 2-1. We had reported that the concentration of Hp 1-1 is significantly and differentially higher than that of Hp 2-1 and 2-2 in normal human subjects. Based on our experimental and theoretical data, we hypothesized that the gene activity of Hp 1 is much more predominant than Hp 2 that is responsible for these differential concentrations as well as the unique assembly of Hp 2-1. Understanding the molecular arrangement in Hp polymers may provide insight into the underlying mechanism by which Hp phenotype is correlated with the development of inflammation-related diseases.