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. 2025 Jul 21;8(7):e71097.
doi: 10.1002/hsr2.71097. eCollection 2025 Jul.

Polymorphic Distribution of Human Homeostatic Iron Regulator Gene H63D rs1799945 and Clinico-Hematological Parameters of Sickle Cell Anemia Patients: A Case-Control Study in Northern Ghana

Samuel Kwasi Appiah  1   2 , Charles Nkansah  1   2 , Samira Daud  1 , Gabriel Abbam  1 , Felix Osei-Boakye  3 , Larry Adom  4 , Rekhiatu Oboirien Abdul Rauf  4 , Godfred Takyi Addae  4 , Lydia Sarpong  4 , Godfred Amoah Appiah  4 , Charles Agnaatah Derigubah  5 , Jennifer Obeng Mensah  4 , Onwuka Chima Kalu  2 , Victor U Usanga  2 , Boniface Nwofoke Ukwah  2 , Ejike Felix Chukwurah  2
Affiliations

Polymorphic Distribution of Human Homeostatic Iron Regulator Gene H63D rs1799945 and Clinico-Hematological Parameters of Sickle Cell Anemia Patients: A Case-Control Study in Northern Ghana

Samuel Kwasi Appiah et al. Health Sci Rep. .

Abstract

Background and aim: The study assessed the polymorphic distribution of H63D rs1799945 of HFE gene and clinico-hematological parameters of SCA patients.

Methods: Sixty sickle cell anemia (SCA) patients and 30 healthy controls without sickle cell disease between the ages of 2-38 years were selected for this case-control study from March to July, 2023 in the Northern Ghana. Ethylenediaminetetraacetic acid (EDTA)-anticoagulated blood samples were used for complete blood count estimation using a 5-part hematology autoanalyzer (URIT-5250 China). Genomic DNA was extracted from whole blood using the spin-column protocol for DNA (Qiagen Kit) and genotyping of H63D rs1799945 gene was performed using Agena MassARRAY with iPLEX PCR (Agena Biosciene, USA).

Results: The median age of the participants was 15.8 (2.0-38.0) years. All the study participants possess only the wild-type allele (CC) of the H63D rs1799945 gene. The mutant variants (CG and GG) were not detected among the study population. There were significant reductions in the RBC (p < 0.001), Hb (p < 0.001), and HCT (p < 0.001), but higher levels of ferritin (p < 0.001), CRP (p < 0.001), MCV (p = 0.001), RDW-CV% (p < 0.001), TWBC (p < 0.001) and platelet count (p = 0.002) in SCA participants than the controls. Incidence of vaso-occlusive crisis (VOC) correlated with increased levels of ferritin (r = 0.458, p < 0.001), CRP (r = 0.461, p < 0.001), platelet (r = 0.537, p < 0.001) and WBC (r = 0.302, p = 0.019) counts but inversely correlated with Hb levels (r = -517, p < 0.001) of SCA patients. Also, levels of ferritin (p < 0.001), Hb (p = 0.001), TWBC (p = 0.018), platelet (p < 0.001), frequencies of VOC (p < 0.001) and number of hospitalization (p < 0.001), were significantly improved in participants on hydroxyurea therapy than the hydroxyurea naïve participants.

Conclusion: The mutant G allele is very rare among the study population. The study also observed severe hematological alterations in SCA participants compared to the controls group. Hydroxyurea was found to improve the clinico-hematological parameters and the need to encourage its usage.

Keywords: homeostatic iron regulator; sickle cell anemia; sickle cell disease; single‐nucleotide polymorphism; vaso‐occlusive crises.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Serum ferritin levels of the study participants stratified by the sickle cell anemia cases and controls.
Figure 2
Figure 2
Relationship of VOC Incidence with levels of Ferritin, Hemoglobin, Platelet and White blood cell count.
See this image and copyright information in PMC

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