Objectives: Sickle cell disease (SCD) has a varied clinical and biological expression depending on the hemoglobin phenotype: SSFA2, SFA2, SAFA2 and SC. Considering the antioxidant properties of the different haptoglobin phenotypes (Hp 1-1, Hp 2-1, Hp 2-2), it seemed relevant to know their influence on the morbidity of the different hemoglobin phenotype of SCD. Thus, the objective of this study was to identify associations between haptoglobin phenotype and morbidity of different SCD phenotypes. Methods: In a retrospective cross-sectional descriptive and analytical study, with a cohort of 170 black African carriers of hemoglobin S, in Ivory Coast, West Africa, hemoglobin and haptoglobin phenotypes were determined by electrophoretic methods. Results: The three major phenotypes of haptoglobin polymorphism were found in the SCD cohort: Hp 1-1 (24.1%), Hp 2-1 (56.5%), Hp 2-2 (19.4%). Vaso-occlusions were associated with haptoglobin phenotype Hp 1-1, (OR = 2.03; CI95% = [1.06 - 3.9]; p < 0.05). Probability of worse morbidity score was 4.55 times greater for hemoglobin phenotype different from SSFA2 (CI95% = [1.43 - 14.44]) and the probability of having the Hp 1-1 phenotype was lower (CI95% = [0.170 - 0.705]). Conclusions: Haptoglobin phenotype was associated to morbidity-adjusted hemoglobin phenotype. The study revealed a greater probability of a worse morbidity when the hemoglobin phenotype is homozygous. Unexpectedly, the worse morbidity is associated to Hp 1-1 haptoglobin phenotype, the most powerful antioxidant within the different haptoglobin phenotypes. Associations found were not systematic and need further studies to enlighten the determinism of SCD morbidity.
References
[1]
Osunkwo, I., Andemariam, B., Minniti, C.P., Inusa, B.P.D., El Rassi, F., Francis-Gibson, B., et al. (2021) Impact of Sickle Cell Disease on Patients’ Daily Lives, Symptoms Reported, and Disease Management Strategies: Results from the International Sickle Cell World Assessment Survey (SWAY). American Journal of Hematology, 96, 404-417. https://doi.org/10.1002/ajh.26063
[2]
Tolo-Diebkilé, A., Koffi, K.G., Nanho, D.C., Sawadogo, D., Kouakou, B., Siransy-Bogui, L., et al. (2010) Homozygous Sickle Cell Disease in Ivorian Adults over 21 Years Old. Cahiers d’études et de recherches francophones/Santé, 20, 63-67. https://doi.org/10.1684/san.2010.0184
[3]
Dubert, M., Elion, J., Tolo, A., Diallo, D.A., Diop, S., Diagne, I., et al. (2017) Degree of Anemia, Indirect Markers of Hemolysis, and Vascular Complications of Sickle Cell Disease in Africa. Blood, 130, 2215-2223. https://doi.org/10.1182/blood-2016-12-755777
[4]
Rees, D.C., Williams, T.N. and Gladwin, M.T. (2010) Sickle-Cell Disease. The Lancet, 376, 2018-2031. https://doi.org/10.1016/S0140-6736(10)61029-X
[5]
Moreira, L.R.S., Miranda-Vilela, A.L., Silva, I.C.R., Akimoto, A.K., et al. (2009) Antioxidant Effect of Haptoglobin Phenotypes against DNA Damage Induced by Hydrogen Peroxide in Human Leukocytes. Genetics and Molecular Research, 8, 284-290. https://doi.org/10.4238/vol8-1gmr569
[6]
Gueye Tall, F., Martin, C., Ndour, E.H.M., Faes, C., Déme Ly, I., Pialoux, V., et al. (2020) Influence of Oxidative Stress Biomarkers and Genetic Polymorphisms on the Clinical Severity of Hydroxyurea-Free Senegalese Children with Sickle Cell Anemia. Antioxidants, 9, Article 863. https://doi.org/10.3390/antiox9090863
[7]
Guéye, P.M., Glasser, N., Férard, G. and Lessinger, J.M. (2006) Influence of Human Haptoglobin Polymorphism on Oxidative Stress Induced by Free Hemoglobin on Red Blood Cells. Clinical Chemistry and Laboratory Medicine, 44, 542-547. https://doi.org/10.1515/CCLM.2006.095
[8]
Naryzny, S.N. and Legina, O.K. (2021) Haptoglobin as a Biomarker. Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry, 15, 184-198. https://doi.org/10.1134/S1990750821030069
[9]
Madkour, M.I., Hassan, R.E., Sherif, N.M., Awadallah, S., Abdelrahim, D.N., Jahrami, H.A., et al. (2022) Haptoglobin Polymorphism Modulates Cardiometabolic Impacts of Four Consecutive Weeks, Dawn to Sunset Ramadan Intermittent Fasting among Subjects with Overweight/Obesity. Diabetes Research and Clinical Practice, 190, Article ID: 110024. https://doi.org/10.1016/j.diabres.2022.110024 https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(22)00838-5/fulltext
[10]
Edwards, O., Burris, A., Lua, J., Wilkie, D.J., Ezenwa, M.O. and Doré, S. (2022) Influence of Haptoglobin Polymorphism on Stroke in Sickle Cell Disease Patients. Genes, 13, Article 144. https://doi.org/10.3390/genes13010144
[11]
Marshall, K., Howell, S., Badaloo, A., Reid, M., McFarlane-Anderson, N. and McKenzie, C. (2018) Exploring Putative Genetic Determinants of Inter-Individual Phenotypic Heterogeneity in Sickle Cell Disease: A Cross-Sectional Jamaican Cohort-Based Study. Blood Cells, Molecules, and Diseases, 73, 1-8. https://doi.org/10.1016/j.bcmd.2018.08.001
[12]
Adekile, A.D. and Haider, M.Z. (2010) Haptoglobin Gene Polymorphisms in Sickle Cell Disease Patients with Different βS-Globin Gene Haplotypes. Medical Principles and Practice, 19, 447-450. https://doi.org/10.1159/000320302
[13]
Louderback, A.L. and Shanbrom, E. (1967) Hemoglobin Electrophoresis. The Journal of the American Medical Association, 202, 718-719. https://doi.org/10.1001/jama.202.8.718
[14]
Engler, R., Rondeau, Y., Pointis, J. and Jayle, M.F. (1973) Peroxydasic Activities of Hemoglobinic Combinations of the Three Haptoglobin Phenotypes. Clinica Chimica Acta, 47, 149-152. https://doi.org/10.1016/0009-8981(73)90309-4
[15]
Koch, W., Latz, W., Eichinger, M., Roguin, A., Levy, A.P., Schömig, A., et al. (2002) Genotyping of the Common Haptoglobin Hp 1/2 Polymorphism Based on PCR. Clinical Chemistry, 48, 1377-1382. https://doi.org/10.1093/clinchem/48.9.1377
[16]
Marks, L.J., Munube, D., Kasirye, P., Mupere, E., Jin, Z., LaRussa, P., et al. (2018) Stroke Prevalence in Children with Sickle Cell Disease in Sub-Saharan Africa: A Systematic Review and Meta-Analysis. Global Pediatric Health, 5, 1-9. https://doi.org/10.1177/2333794X18774970
Desai, R.J., Mahesri, M., Globe, D., Mutebi, A., Bohn, R., Achebe, M., et al. (2020) Clinical Outcomes and Healthcare Utilization in Patients with Sickle Cell Disease: A Nationwide Cohort Study of Medicaid Beneficiaries. Annals of Hematology, 99, 2497-2505. https://doi.org/10.1007/s00277-020-04233-w
[19]
Diop, S., Mokono, S.O., Ndiaye, M., Touré Fall, A.O., Thiam, D. and Diakhaté, L. (2003) Homozygous Sickle Cell Disease in Patients above 20 Years of Age: Follow-up of 108 Patients in Dakar. La Revue de Médecine Interne, 24, 711-715. https://doi.org/10.1016/S0248-8663(03)00220-0
[20]
Perry Caldwell, E. and Killingsworth, E. (2021) The Health Literacy Disparity in Adolescents with Sickle Cell Disease. Journal for Specialists in Pediatric Nursing, 26, e12353. https://onlinelibrary.wiley.com/doi/10.1111/jspn.12353 https://doi.org/10.1111/jspn.12353
[21]
Daak, A.A., Elsamani, E., Ali, E.H., Mohamed, F.A., Abdel-Rahman, M.E., Elderdery, A.Y., et al. (2016) Sickle Cell Disease in Western Sudan: Genetic Epidemiology and Predictors of Knowledge Attitude and Practices. Tropical Medicine & International Health, 21, 642-653. https://doi.org/10.1111/tmi.12689
[22]
Baltierra, D., Harper, T., Jones, M.P. and Nau, K.C. (2015) Hematologic Disorders: Sickle Cell Disease. FP Essentials, 433, 27-39.
[23]
Keber, B., Lam, L., Mumford, J. and Flanagan, B. (2019) Hematologic Conditions: Common Hemoglobinopathies. FP Essentials, 485, 24-31.
[24]
Ko, D.H., Chang, H.E., Kim, T.S., Song, E.Y., Park, K.U., Song, J., et al. (2013) A Review of Haptoglobin Typing Methods for Disease Association Study and Preventing Anaphylactic Transfusion Reaction. BioMed Research International, 2013, Article ID: 390630. https://doi.org/10.1155/2013/390630
[25]
Meher, S., Mohanty, P.K., Patel, S., Das, K., Sahoo, S., Dehury, S., et al. (2021) Haptoglobin Genotypes Associated with Vaso-Occlusive Crisis in Sickle Cell Anemia Patients of Eastern India. Hemoglobin, 45, 358-364. https://doi.org/10.1080/03630269.2020.1801459
[26]
Kengne Fotsing, C.B., Pieme, C.A., Biapa Nya, P.C., Chedjou, J.P., Dabou, S., Nguemeni, C., et al. (2022) Relation between Haptoglobin Polymorphism and Oxidative Stress Status, Lipid Profile, and Cardiovascular Risk in Sickle Cell Anemia Patients. Health Science Reports, 5, e465. https://doi.org/10.1002/hsr2.465
