Background: In Côte d’Ivoire so
far, the circulating haplotypes have been inferred on the phenotypic profiling
of SCD patients. The impact of the circulating haplotypes on the use of
Hydroxyurea has not been assessed yet. Therefore the objective of this study is
to identify in Abidjan the HbS haplotypes that modulate HU treatment responses. Methods: In a cross-sectional descriptive and analytical study, children
aged 5 to 15 years with SCD, and carrying the hemoglobin phenotypes SSFA2 and
SFA2, were recruited into a HU treatment cohort. Various parameters on the
haplotypes and the outcomes of the treatment were analyzed. Results: Thirty nine children with SCD were included. The phenotypic profile of the cohort
was 86.6% of SSFA2 and 15.4% of SFA2. Three haplotypes were found, the Benin
haplotype, the Senegal haplotype, and an atypical one. The participants
belonged to three genotypes, Benin/atypical
(64.1%), Benin/Senegal (33.3%) and Senegal/Senegal (2.6%). Overall, HU
treatment was successful in all haplotypes with 12 out of 39 patients failing
treatment after 12 months in the Benin haplotype group. The association between
HU treatment success and the Benin haplotype was found in terms of the decrease
in the number of white blood cells and the students missing class. Conclusion: The study revealed that inferring haplotype based on the phenotypic profile
could be inaccurate. The proportion of atypical haplotype that were not
previously described in Côte d’Ivoire was high. All the haplotypes seemed to be associated with HU
treatment success but some patients with Benin haplotype did not respond well.
Chang, A.K., Ginter Summarell, C.C., Birdie, P.T. and Sheehan, V.A. (2018) Genetic Modifiers of Severity in Sickle Cell Disease. Clinical Hemorheology and Microcirculation, 68, 147-164. https://doi.org/10.3233/CH-189004
[3]
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
[4]
Mcgann, P.T., Ferris, M.G., Ramamurthy, U., Santos, B., de Oliveira, V., Bernardino, L. and Ware, R.E. (2013) A Prospective Newborn Screening and Treatment Program for Sickle Cell Anemia in Luanda, Angola. American Journal of Hematology, 88, 984-989. https://doi.org/10.1002/ajh.23578
[5]
Chang, Y., Smith, K.D., Moore, R., et al. (1995) An Analysis of Fetal Hemoglobin Variation in Sickle Cell Disease: The Relative Contributions of the X-Linked Factor, β-Globin Haplotypes, α-Globin Gene Number, Gender, and Age. Blood, 85, 1111-1117. https://doi.org/10.1182/blood.V85.4.1111.bloodjournal8541111
[6]
Green, N.S., Fabry, M.E., Kaptue-Noche, L., et al. (1993) Senegal Haplotype Is Associated with Higher HbF than Benin and Cameroon Haplotypes in African Children with Sickle Cell Anemia. American Journal of Hematology, 44, 145-146. https://doi.org/10.1002/ajh.2830440214
[7]
Habara, A. and Steinberg, M.H. (2016) Minireview: Genetic Basis of Heterogeneity and Severity in Sickle Cell Disease. Experimental Biology and Medicine, 241, 689-696. https://doi.org/10.1177/1535370216636726
[8]
Montalembert, M., Brousse, V., Marchetti, M.T. and Allali, S. (2020) La drépanocytose de l’enfant et l’adolescent. Elsevier Masson, Maryland.
[9]
Mabiala-Babela, J.R., Nika, E.R., Ikobo, L.C.O., Gnakingue, A.N.O., Ngoulou, B.P.S. and Mandilou, S.V.M. (2019) Le devenir des enfants atteints de drépanocytose homozygote traités par hydroxyurée à Brazzaville (Congo). Bulletin de la Société De Pathologie Exotique, 112, 206-212. https://doi.org/10.3166/bspe-2019-0096
[10]
Charache, S., Dover, G.J., Moore, R.D., Eckert, S., Ballas, S.K., Koshy, M., Milner, P.F.A., Orringer, E.P., Phillips Jr., G., Platt, O.S. and Thomas, G.H. (1992) Hydroxyurea: Effects on Hemoglobin F Production in Patients with Sickle Cell Anemia. Blood, 79, 2555-2565. https://doi.org/10.1182/blood.V79.10.2555.2555
[11]
Jayabose, S., Tugal, O., Sandoval, C., Patel, P., Puder, D., Lin, T. and Visintainer, P. (1996) Clinical and Hematologic Effects of Hydroxyurea in Children with Sickle Cell Anemia. The Journal of Pediatrics, 129, 559-565. https://doi.org/10.1016/S0022-3476(96)70121-X
[12]
Ali, M.A., Ahmad, A., Chaudry, H., Aiman, W., Aamir, S., Anwar, M.Y. and Khan, A. (2020) Efficacy and Safety of Recently Approved Drugs for Sickle Cell Disease: A Review of Clinical Trials. Experimental Hematology, 92, 11-18. https://doi.org/10.1016/j.exphem.2020.08.008
[13]
Karamperis, K., Tsoumpeli, M.T., Kounelis, F., Koromina, M., Mitropoulou, C., Moutinho, C. and Patrinos, G.P. (2021) Genome-Based Therapeutic Interventions for β-Type Hemoglobinopathies. Human Genomics, 15, Article No. 32. https://doi.org/10.1186/s40246-021-00329-0
[14]
Husain, M., Hartman, A.D. and Desai, P. (2017) Pharmacogenomics of Sickle Cell Disease: Steps toward Personalized Medicine. Pharmacogenomics and Personalized Medicine, 10, 261-265. https://doi.org/10.2147/PGPM.S123427
[15]
Rigano, P., De Franceschi, L., Sainati, L., Piga, A., Piel, F.B., Cappellini, M.D., Fidone, C., Masera, N., Palazzi, G., Gianesin, B., et al. (2018) Real-Life Experience with Hydroxyurea in Sickle Cell Disease: A Multicenter Study in a Cohort of Patients with Heterogeneous Descent. Blood Cells, Molecules, and Diseases, 69, 82-89. https://doi.org/10.1016/j.bcmd.2017.08.017
[16]
Ribeiro, P.R., Teixeira, R.D.S., Souza, A.R., Pereira, T.C.S., Boffo, E.F., Carosio, M.G.A., Ferreira, A.G., Oliveira, R.V., Rodrigues, L.E.A., Silva, J.D.J., et al. (2021) Blood Plasma Metabolomics of Children and Adolescents with Sickle Cell Anaemia Treated with Hydroxycarbamide: A New Tool for Uncovering Biochemical Alterations. British Journal of Haematology, 192, 922-931. https://doi.org/10.1111/bjh.17315
[17]
Ma, Q., Wyszynski, D.F., Farrell, J.J., Kutlar, A., Farrer, L.A., Baldwin, C.T. and Steinberg, M.H. (2007) Fetal Hemoglobin in Sickle Cell Anemia: Genetic Determinants of Response to Hydroxyurea. The Pharmacogenomics Journal, 7, 386-394. https://doi.org/10.1038/sj.tpj.6500433
[18]
Chand, A.R., Xu, H., Wells, L.G., Clair, B., Neunert, C., Spellman, A.E., Clay, L.J., Natrajan, K. and Kutlar, A. (2014) Are There True Non-Responders to Hydroxyurea in Sickle Cell Disease? A Multiparameter Analysis. Blood, 124, 4073. https://doi.org/10.1182/blood.V124.21.4073.4073
[19]
Louderback, A.L. and Shanbrom, E. (1967) Hemoglobin Electrophoresis. JAMA, 202, 718-719. https://doi.org/10.1001/jama.202.8.718
[20]
Koui, T.A.S., Gnondjui, A.A., Gbessi, A.E., Ako, A.A.B., Coulibaly, B., Aka, A.D., et al. (2022) High Level of Heterozygous Haplotype of Hemoglobin in Abidjan Population with Mild Malaria. BMC Medical Genomics, 15, Article No. 120. https://doi.org/10.1186/s12920-022-01263-3
[21]
Akinsheye, I., Alsultan, A., Solovieff, N., et al. (2011) Fetal Hemoglobin in Sickle Cell Anemia. Blood, 118, 19-27. https://doi.org/10.1182/blood-2011-03-325258
[22]
Bhagat, S., Patra, P.K. and Thakur, A.S. (2013) Fetal Haemoglobin and β-Globin Gene Cluster Haplotypes among Sickle Cell Patients in Chhattisgarh. Journal of Clinical and Diagnostic Research, 7, 269-272. https://doi.org/10.7860/JCDR/2013/4381.2744
[23]
Sheehan, V.A., Luo, Z., Flanagan, J.M., Howard, T.A., Thompson, B.W., Wang, W.C., Kutlar, A. and Ware, R.E. (2013) Genetic Modifiers of Sickle Cell Anemia in the Baby Hug Cohort: Influence on Laboratory and Clinical Phenotypes. American Journal of Hematology, 88, 571-576. https://doi.org/10.1002/ajh.23457
[24]
Menzel, S. and Thein, S.L. (2019) Genetic Modifiers of Fetal Haemoglobin in Sickle Cell Disease. Molecular Diagnosis & Therapy, 23, 235-244. https://doi.org/10.1007/s40291-018-0370-8
[25]
Rahimy, M.C., Gangbo, A., Ahouignan, G., et al. (2003) Effect of a Comprehensive Clinical Care Program on Disease Course in Severely Ill Children with Sickle Cell Anemia in a Sub-Saharan African Setting. Blood, 102, 834-838. https://doi.org/10.1182/blood-2002-05-1453
[26]
Molineaux, L., Fleming, A.F., Cornille-Brogger, R., Kagan, I. and Storey, J. (1979) Abnormal Haemoglobins in the Sudan Savanna of Nigeria. III. Malaria, Immunoglobulins and Antimalarial Antibodies in Sickle Cell Disease. Annals of Tropical Medicine & Parasitology, 73, 301-310. https://doi.org/10.1080/00034983.1979.11687263
[27]
Piel, F.B., Hay, S.I., Gupta, S., Weatherall, D.J. and Williams, T.N. (2013) Global Burden of Sickle Cell Anaemia in Children under Five, 2010-2050: Modelling Based on Demographics, Excess Mortality, and Interventions. PLOS Medicine, 10, e1001484. https://doi.org/10.1371/journal.pmed.1001484
[28]
Ngo, D., Bae, H., Steinberg, M.H., et al. (2013) Fetal Hemoglobin in Sickle Cell Anemia: Genetic Studies of the Arab-Indian Haplotype. Blood Cells, Molecules & Diseases, 51, 22-26. https://doi.org/10.1016/j.bcmd.2012.12.005
