HEMOGLOBIN RALEIGH & FALSELY ELEVATED HBA1C IN AUTOMATED ION-EXCHANGE HPLC

血红蛋白罗利

• 批准号: 6118621
• 负责人: DAN CHEN
• 金额: $ 0.16万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6118621
• 关键词: biomedical resource; genetics; hematology; human subject; male; proteins; spectrometry

Irreversible glycation of the HbA0( chain leads to the production of HbA1C, which can be used to monitor long-term blood glucose control in patients with diabetes mellitus. HbA1C is less positively charged than non-glycated HbA0 and this decrease in charge is the basis of ion-exchange and electrophoretic methods that measure HbA1C. We recently identified a sample that appeared to contain 46% HbA1C by an automated ion-exchange HPLC method (Bio-Rad Variant) but only 3.8% by an immuno-inhibition latex agglutination method. A combination of traditional and mass spectrometric protein analysis and genomic DNA analysis of the Hb ( chain and genes revealed that the patient was heterozygote for Hb-Raleigh, a variant containing a valine->alanine substitution at position 1 of the ( chain. The amino-terminal alanine in this variant Hb is posttranslationally modified by acetylation leading to a charge difference similar to glycation, making the behavior of HbA1C and Hb Raleigh virtu ally identical in the ion-exchange HPLC method. This observation suggests that it is important to confirm HbA1C values in excess of 15%, especially if they are not consistent with clinical picture, by an independent HbA1C method, such as an immunoassay or boronic acid affinity chromatography. However, for this particular variant Hb even these latter methods might be misleading since the acetylated N-terminal amino acid of the Hb-Raleigh ( chain cannot be glycated.

HbA 0（链）的不可逆糖化导致产生 HbA 1C，可用于监测长期血糖控制 在糖尿病患者中。 HbA 1C的正电荷较少 比非糖化HbA 0，这种电荷的减少是基础 离子交换和电泳方法测量HbA 1C。 我们 最近发现一个样本，似乎含有46%的HbA 1C， 自动离子交换HPLC法（Bio-Rad变体），但仅3.8%， 一种免疫抑制乳胶凝集法， 的组合 传统和质谱蛋白质分析和基因组DNA Hb（链和基因的分析显示，患者 Hb-Raleigh杂合子，一种含有缬氨酸->丙氨酸的变体 在（链的位置1处的取代。 氨基末端丙氨酸 在该变体中，Hb通过乙酰化进行后修饰 导致类似于糖基化的电荷差异， HbA 1C和Hb罗利的行为在 离子交换HPLC法。 这一观察表明，它是 确认HbA 1C值超过15%很重要，特别是如果 与临床表现不一致，通过独立HbA 1C 方法，如免疫测定或硼酸亲和 层析 然而，对于这种特定的血红蛋白变体，即使这些 后一种方法可能会产生误导，因为乙酰化的N-末端 Hb-Raleigh链的氨基酸不能被糖化。