Liu Zhongwei, Feng Du, Gu Danshan, Zheng Richard, Esperat Christina, Gao Weimin
Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, Lubbock, TX.
School of Nursing, University of Nevada, Las Vegas, NV.
Biofactors. 2017 May 6;43(3):424-433. doi: 10.1002/biof.1352. Epub 2017 Feb 20.
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.
糖化血红蛋白（HbA1c）检测目前是诊断2型糖尿病（T2DM）的主要工具，尤其是用于评估慢性高血糖。然而，许多研究报道了使用HbA1c进行T2DM诊断/预后评估的局限性，例如敏感性差、标准化困难以及不同种族群体的切点不同。因此，本研究的目的是发现与HbA1c水平升高相关的新型生物标志物，作为T2DM的辅助诊断工具。二维差异凝胶电泳结合质谱法用于分别从糖化血红蛋白≥7和糖化血红蛋白<7的西班牙裔T2DM受试者（n = 74）收集的两份混合血清样本的蛋白质谱分析。与糖化血红蛋白<7的受试者相比，糖化血红蛋白≥7的T2DM受试者的混合血清样本中触珠蛋白（Hp）α1/α2链的亚型有显著改变。通过聚合酶链反应和蛋白质印迹分析进一步确定了262名西班牙裔受试者的Hp基因型，其中包括109名T2DM患者和153名非糖尿病对照。同时，还建立了一种新的用于Hp基因分型的液滴数字聚合酶链反应方法。与非糖尿病对照相比，T2DM患者中Hp2等位基因的分布更高，并且携带至少一个Hp2等位基因的T2DM患者的糖化血红蛋白水平往往高于Hp 1-1的T2DM患者。总之，我们的结果表明，差异表达的血清Hp蛋白亚型可能与糖化血红蛋白水平相关，并且在西班牙裔人群中携带Hp2等位基因的受试者发生T2DM的风险更高。© 2016生物因子，43(3):424 - 433，2017。
