Abstract
β-S globin haplotype (βS haplotype) characterization in sickle cell anemia (SCA) patients is important because it assists individualized treatment. However, the patient with atypical haplotypes do not present detailed studies such as clinical and laboratory data. To understand the phenotypic expression of atypical haplotype patients in relation to typical haplotype ones, it may be necessary to assess the main clinical and laboratorial parameters and investigate transcription factors, as possible genetic modulators that can contribute to the improvement of the SCA patients’ clinical condition. The study group was composed of 600 SCA Brazilian patients of both genders ranging in age from 1 to 68 years. The atypical haplotypes were the third most frequent (5.7%) with 11 patterns numerically ranked according to occurrence. We verified that patients with atypical 1 haplotype in combination with Bantu haplotype presented milder clinical outcomes in relation to Bantu/Bantu and Benin/Benin patients, according to improved values of hemoglobin and hematocrit. In clinical severity, we did not observe significant statistical differences between typical and atypical haplotype patients, and this result can be explained with reference to the action of transcription factors in β-globin cluster. Thus, we presented the atypical haplotype relationship with SCA pathophysiology, reinforcing the hypothesis that individual genetic factors may be responsible for phenotypic diversity of the disease.
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Acknowledgements
We would like to thank Izabella Luisa Tambones (Department of Biology, São Paulo State University – UNESP) for her technical assistance in transcription factors analyses and Joseph People (Department of Physiology, Development and Neuroscience, University of Cambridge) for English proofreading. The Pro-Institute of Hematology Foundation (Fundarj) and the State of Sao Paulo Research Foundation (FAPESP process number 2011/14168-5) for the financial support. Silva is a partnership member of Redoxoma – CEPID/FAPESP (2013/07937-8).
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Okumura, J.V., Silva, D.G.H., Torres, L.S. et al. Atypical β-S haplotypes: classification and genetic modulation in patients with sickle cell anemia. J Hum Genet 64, 239–248 (2019). https://doi.org/10.1038/s10038-018-0554-4
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DOI: https://doi.org/10.1038/s10038-018-0554-4
