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Short Communication Volume 13 Issue 1
Linking fetal hemoglobin gamma - chain variants to gestational diabetes: a CRISPR–Cas9 investigative model
Mosab Nouraldein Mohammed Hamad, Sufian KM Nor
Received: March 08, 2026 | Published: March 23, 2026
Citation: Hamad MNM, Nor SKM. Linking fetal hemoglobin gamma - chain variants to gestational diabetes: a CRISPR–Cas9 investigative model. J Diabetes Metab Disord Control. 2026;13(1):38-39. DOI: 10.15406/jdmdc.2026.13.00310
Abstract
Gestational diabetes mellitus (GDM) is characterized by progressive insulin resistance and enhanced hepatic gluconeogenesis during pregnancy. Elevated alanine aminotransferase (ALT) levels are associated with increased GDM risk. Fetal hemoglobin (HbF, α₂γ₂) contains γ-globin variants at position 136, where glycine (Gγ) or alanine (Aγ) residues are present. We propose that γ-chain composition may influence erythrocyte metabolic function and indirectly modulate systemic alanine–pyruvate flux rather than serving as a direct amino acid source. This hypothesis integrates γ-globin polymorphisms with erythrocyte metabolic signaling, ALT-mediated alanine transamination, and hepatic metabolic adaptation during pregnancy. A CRISPR–Cas9 investigative framework is proposed using patient-derived CD34⁺ hematopoietic stem and progenitor cells (HSPCs) from women with GDM. Multiple genome-editing strategies—including HBG1 knock-in, BCL11A erythroid enhancer disruption, and promoter editing—are discussed. Evaluation of metabolic flux, insulin signaling, and erythroid function, alongside assessment of long-term efficacy and safety, may provide insight into a previously unexplored link between fetal hemoglobin composition and gestational metabolic dysregulation.
Keywords: Gamma-globin variants, alanine–pyruvate metabolism, erythrocyte metabolism, CRISPR–Cas9 genome editing
©2026 Hamad, et al. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.