Functional characterization of compound heterozygosity Hb S/Hb Deer Lodge in Brazil

Marcondes J Sobreira; Thais H Batista; Rodrigo M Santana; Gabriela S Arcanjo; Susan E Jorge; Magnun N Santos; Dulcinéia M Albuquerque; Betânia L Hatzlhofer; Ana C Dos Anjos; Fernando F Costa; Aderson S Araujo; Maria F Sonati; Antonio R Lucena-Araujo; Marcos A Bezerra

doi:10.1016/j.htct.2023.09.2370

Functional characterization of compound heterozygosity Hb S/Hb Deer Lodge in Brazil

Hematol Transfus Cell Ther. 2023 Dec 7:S2531-1379(23)02594-4. doi: 10.1016/j.htct.2023.09.2370. Online ahead of print.

Authors

Affiliations

¹ Universidade Federal de Pernambuco, Programa de Pós-Graduação em Genética, Recife, PE, Brasil.
² Universidade de Campinas, Faculdade de Ciências Médicas, Departamento de Patologia Clínica, Campinas, SP, Brasil.
³ Universidade de Campinas, Centro de Hematologia e Hemoterapia, Campinas, SP, Brasil.
⁴ Universidade Federal de Pernambuco, Programa de Pós-Graduação em Genética, Recife, PE, Brasil; Universidade Federal de Pernambuco, Centro de Ciências da Saúde, Departamento de Ciências Farmacêuticas, Recife, PE, Brasil.
⁵ Fundação de Hematologia e Hemoterapia de Pernambuco, Departamento de Medicina Interna, Recife, PE, Brasil.
⁶ Universidade Federal de Pernambuco, Programa de Pós-Graduação em Genética, Recife, PE, Brasil. Electronic address: macbezerra.ufpe@gmail.com.

PMID: 38307823
DOI: 10.1016/j.htct.2023.09.2370

Abstract

Introduction: The Hb Deer Lodge (β2 His>Arg; HBB:c.8A>G) is a structural hemoglobin variant described in some populations around the world, characterized by increased oxygen affinity, but does not confer clinical symptoms to its carriers. The coinheritance of the Hb Deer Lodge with the most common hemoglobin variant, Hb S, has been reported only once; however, functional data were not described. Here we show a case of the Hb S and Hb Deer Lodge carrier in heterozygosity.

Methods: The Hb S and Hb Deer Lodge association was identified by High-Performance Liquid Chromatography (HPLC), reverse phase HPLC and the β globin gene sequencing. The functional characterization of this interaction was obtained using the O₂ dissociation curve, determination of the cooperativity between the globin chains and the Bohr effect in the presence and absence of organic phosphates.

Results: When the Hb S and Hb Deer Lodge were associated, there was a decrease in cooperativity, no significant changes in oxygen affinity and no significant Bohr effect changes.

Conclusion: Despite these genetic variations, the carrier showed no hematological alterations and no clinical symptoms, possibly due to the high oxygen affinity of the Hb Deer Lodge, which interferes with the Hb S polymerization.

Keywords: Hemoglobin Deer Lodge; Hemoglobin variant; Sickle cell disease.