Relationship between Hpt polymorphisms and serum protein electropherogram

Serum protein electrophoresis is routinely used to identify pathologies involving dysproteinemia. The electropherogram mainly represents the most abundant serum proteins, one of which is the polymorphic haptoglobin (Hpt), characterized by a molecular heterogeneity with three major phenotypes (Hpt 1-1, 2-1, and 2-2). To improve the interpretation of electropherogram and possibly to extend its applicability, we aimed to explore the relationship between Hpt phenotypes (determined by immunoblotting) and protein profiles. Serum samples were separated by CZE with PROTEIN 6 and high-resolution methods. The PROTEIN 6 analysis showed significant associations between alpha2 zone profiles and Hpt phenotypes (chi-square=154.06, p<0.0001). The high-resolution method indicated significant differences between Hpt 2-2 and Hpt 1-1 peak mobilities, evidenced by receiver operating characteristic analysis, (area under the receiver operating characteristic curve=0.98, p<0.0001, standard error=0.01346, likelihood ratios=21.39), with 98.7% sensitivity, and 95.4% specificity. However, the structural heterogeneity of Hpt 2-1 made it difficult to relate with a particular profile. Thus, we developed an alternative approach that excluded the Hpt 1-1 or Hpt 2-2 phenotypes. This may prove to be a useful technique in clinical applications considering the involvement of Hpt 2-2 or Hpt 1-1 in various pathologies.