HEMOGLOBIN RALEIGH AS CAUSE OF FALSELY ELEVATED HBA1C IN AN AUTOMATED ION

由于自动离子检测中 HBA1C 错误升高而导致血红蛋白 RALEIGH

• 批准号: 6665806
• 负责人: DAN CHEN
• 金额: $ 15.75万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6665806
• 关键词: biomedical resource; child (0-11); female; health care; human tissue; neoplasm /cancer; nucleic acids; reproductive system; spectrometry

Irreversible glycation of the HbA0( chain leads to the productin 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 immunoinhibition 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 Raleig h virtual ly 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.

HbA0( 链的不可逆糖化导致产生 HbA1C，可用于监测长期血糖控制情况 糖尿病患者。 HbA1C 的正电荷较少 与非糖化 HbA0 相比，电荷的减少是 测量 HbA1C 的离子交换和电泳方法。 我们 最近，一位研究人员发现了一份似乎含有 46% HbA1C 的样本 自动离子交换 HPLC 方法（Bio-Rad Variant），但只有 3.8% 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（链和基因分析显示，该患者患有 Hb-Raleigh 杂合子，一种包含缬氨酸->丙氨酸的变体 ( 链的位置 1 发生取代。氨基末端丙氨酸 在此变体中，Hb 通过乙酰化进行翻译后修饰 导致类似于糖化的电荷差异，使得 HbA1C 和 Hb Raleig h 的行为在 离子交换高效液相色谱法。 这一观察结果表明， 确认 HbA1C 值超过 15% 很重要，特别是如果 独立 HbA1C 与临床表现不一致 方法，例如免疫测定或硼酸亲和力 色谱法。 然而，对于这个特定的 Hb 变体，甚至这些 后一种方法可能会产生误导，因为乙酰化的 N 末端 Hb-Raleigh ( 链的氨基酸不能糖化。