Differentially expressed haptoglobin as a potential biomarker for type 2 diabetic mellitus in Hispanic population

Glycosylated hemoglobin (HbA1c) measurement is currently a primary tool for diagnosis of type 2 diabetes mellitus (T2DM), especially for the assessment of chronic hyperglycemia. However, many studies reported the limitation of using HbA1c for T2DM diagnosis/prognosis, such as poor sensitivities, difficult standardization, and variable cut points across ethnic groups. Therefore, the aim of this study was to discover novel biomarkers associated with elevated HbA1c levels as complementary T2DM diagnostic tools. Two-dimensional difference gel electrophoresis combined with mass spectrometry were applied for protein profile analyses of two pooled serum samples collected from Hispanic T2DM subjects (n = 74) with HbA1c ≥7 and HbA1c< 7, respectively. Isoforms of haptoglobin (Hp) α1/α2 chains were significantly altered in pooled serum samples from T2DM subjects with HbA1c ≥7 compared to those with HbA1c< 7. Hp genotypes of 262 Hispanic subjects, including 109 T2DM and 153 nondiabetic controls, were further determined by PCRs and western blotting analysis. Meanwhile, a new droplet digital PCR method for Hp genotyping was also established. The distribution of Hp2 allele was higher in T2DM subjects compared to nondiabetic controls and the HbA1c levels of T2DM subjects carrying at least one Hp2 allele tended to be higher than T2DM subjects with Hp 1-1. In summary, our results indicate that differentially expressed serum Hp protein isoforms could be associated with HbA1c levels and subjects with Hp2 allele have a higher risk for the occurrence of T2DM in Hispanic population. © 2016 BioFactors, 43(3):424-433, 2017.