Genetic determinants of variability in glycated hemoglobin (HbA 1c) in humans: Review of recent progress and prospects for use in diabetes care

Abstract

Glycated hemoglobin A 1c (HbA 1c) indicates the percentage of total hemoglobin that is bound by glucose, produced from the nonenzymatic chemical modification by glucose of hemoglobin molecules carried in erythrocytes. HbA 1c represents a surrogate marker of average blood glucose concentration over the previous 8 to 12 weeks, or the average lifespan of the erythrocyte, and thus represents a more stable indicator of glycemic status compared with fasting glucose. HbA 1c levels are genetically determined, with heritability of 47% to 59%. Over the past few years, inroads into understanding genetic predisposition by glycemic and nonglycemic factors have been achieved through genome-wide analyses. Here I review current research aimed at discovering genetic determinants of HbA 1c levels, discussing insights into biologic factors influencing variability in the general and diabetic population, and across different ethnicities. Furthermore, I discuss briefly the relevance of findings for diabetes monitoring and diagnosis. © 2011 The Author(s).