Incidence of variant hemoglobin (Hb) and increased fetal Hb concentrations and their effect on Hb A1c measurement in a Korean population.

To the Editor: Glycohemoglobin assays are important for evaluating long-term glycemic control in patients with diabetes (1 ). Ion-exchange HPLC is commonly used for measuring hemoglobin A1c (Hb A1c), but hemoglobin variants (Hb) or increased fetal Hb concentrations may affect the quantification of Hb A1c by HPLC. The presence of Hb or high Hb F concentrations can be recognized by the separate elution of variant peaks or by abnormally high peaks on HPLC, and these abnormal findings arise mostly from genetic alterations in the globin genes (2, 3). In Koreans, only limited data are available on the incidence and molecular genetic background of Hb and high Hb F concentrations. We therefore investigated patients who had abnormal peaks on their Hb A1c analyses and characterized them by molecular methods. Of the 27 006 patients who were tested for Hb A1c at Samsung Medical Center in Seoul, Korea, from May 2004 to October 2004, we investigated 25 patients who had abnormal results [variant peaks or high Hb F values ( 5%)] on the Bio-Rad Variant II Turbo HPLC System. We carried out DNA studies of the globin genes by PCR and sequencing of all the coding exons, promoters, and introns of the -, 1-, 2-, A -, and G -globin genes (4, 5). In the group with increased Hb F, we performed a gene dosage analysis on exon 1 of the -globin gene with the LightCycler (Roche Diagnostics), with albumin coamplified as the reference gene. Ten patients had variant peaks (Fig. 1). Among them, 5 patients had variant peaks between the A1c and A0 peaks (mean retention time, 0.73 min), which were identified as Hb G Coushatta ( 22Glu3Ala). One patient with variant peaks at the E, D window (retention time, 0.87 min)