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的不可逆糖基化(链导致产物 HbA1C，可用于监测长期血糖控制 在糖尿病患者中。HbA1c的正电荷较少 比非糖化的HbA0和这种电荷的减少是基础 测定HbA1C的离子交换和电泳法。我们 最近通过一种方法确定了一个似乎含有46%HbA1C的样本 自动离子交换高效液相色谱法(Bio-Rad变体)，但只有3.8% 一种免疫抑制乳胶凝集法。一种组合 传统和质谱学蛋白质分析与基因组DNA 对Hb(链)和基因的分析表明，患者是 HB-Raleigh杂合子，一种含有Valine-&丙氨酸的变体 在(链的位置1处的替换。氨基末端丙氨酸 在这个变体中，Hb通过乙酰化被翻译后修饰 导致类似于糖基化的电荷差异，使 HbA1C和Hb Raleig h的行为在 离子交换高效液相色谱法。这一观察表明，它是 确认HbA1C值超过15%很重要，特别是在 与临床情况不符，由独立的HbA1C 方法，如免疫分析或硼酸亲和 层析法。然而，对于这种特殊的Hb变种，即使是这些 后一种方法可能具有误导性，因为乙酰化的N-末端 Hb-Raleigh的氨基酸(链不能糖化。