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Productin HBA1C的of，可用于监测长期血糖控制 糖尿病患者。 HBA1C的充电不足 比非糖化的HBA0，收费的减少是 测量HbA1c的离子交换和电泳方法。 我们 最近确定了一个样本，该样本似乎包含46％的HBA1C 自动离子交换HPLC方法（Bio-Rad变体），但仅3.8％ 免疫抑制乳胶凝集法。 组合 传统和质谱蛋白分析和基因组DNA HB的分析（链和基因表明患者是 HB-Raleigh的杂合子，一种含有Valine->丙氨酸的变体 在该位置1的位置（链。氨基末端丙氨酸）的替换 在这种变体中，HB通过乙酰化在翻译后修饰 导致电荷差异类似于糖基，使得 HBA1C和HB Raleig H的行为在 离子交换HPLC方法。 这个观察表明是 重要的是确认超过15％的HBA1C值，尤其是 独立的HBA1C与临床图片不一致 方法，例如免疫测定或硼酸亲和力 色谱法。 但是，对于这种特定的变体HB即使这些 后一种方法可能会产生误导，因为乙酰化的N端 HB-Raleigh的氨基酸（无法糖化链。