Association between global DNA methylation pattern and some haematological parameters in sickle cell subjectsS
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Abstract
Background: DNA methylation mechanisms have been implicated in the conversion of HbF to adult haemoglobin and the presence of HbF in sickle cell disease has been reported as good prognostic marker. The objective of this study was to determine the activities of DNA methyltransferase 1 in sickle cell subjects.
Methods: A case-control study was conducted among the sickle cell patients attending Haematology Clinic in Obafemi Awolowo University Teaching Hospital, Ile-Ife and Ladoke Akintola Teaching Hospital, Osogbo. One hundred subjects were recruited for this study. Sixty (60) were sickle cell subjects while 40 were homozygous AA control.
Results: The results showed that DNA methyltransferase 1 activity in SCD subjects (2.347±0.2472) was significantly lower (p<0.0001) when compared to control (10.39±2.229). Also total white cell count was significantly higher (p=0.0305) in sickle cell subjects (11.53±1.126) when compared to controls (5.39±0.326). Packed cell volume (25.4±0.5601), haemoglobin concentration (8.468±0.1863), red blood cell count (3.462±0.1035) and MCHC (334.9±5.755) were all significantly lower (p<0.0001) in sickle cell subjects when compared to controls (PCV (38.3±0.4955); HB (12.83±0.1814); RBC (5.58±0.07424); MCHC (383.9±3.25) respectively. Furthermore, SCD subjects on hydroxyurea (2.342±0.8018) had a significantly lower (p<0.0001) DNA methyltransferase 1 activity when compared to SCD subjects on L-glutamine (7.567±0.9179). Those on L-glutamine also had a significantly higher (p<0.0001) DNA methyltransferase 1 activities when compared to Crizanlizumab (1.814±0.883), Voxelotor (2.757±1.054), folic acid (2.151±0.245) and pain medication (2.163±0.240.
Conclusion: In conclusion, DNA methyltransferase 1 activity was lower in SCD subjects, especially in subjects on hydroxyurea, crizanlizumab and voxelotor.
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References
Akinbami, A., Dosunmu, A., Adediran, A., Oshinaike, O., Phillip, A., Vincent, O., Olanrewaju, A., and Oluwaseun, A.; (2012); Steady state hemoglobin concentration and packed cell volume in homozygous sickle cell disease patients in Lagos, Nigeria; Caspian Journal of Internal Medicine; 3(2): 405–409.
Bradner, J.E., Mak, R. and Tanguturi, S.K.; (2010); Chemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell disease; Proceedings National Academy of Science USA; 107(28): 12617-12622.
Brahme, K., Mehta, K., Shringarpure, K. and Parmar, M.; (2016); Clinical profile of Sickle Cell Disease patients coming to a tertiary care hospital from central Gujarat; International Journal of Resource Medicine; 5(2): 161-164.
Ekvall, H., Arese, P., Turrini, F., Ayi, K., Mannu, F. and Premji, Z.; (2001); Acute haemolysis in childhood falciparum malaria; Transaction of Royal Society of Tropical Medicine and Hygiene; 95(6): 611–617.
Estepp, J.H., Smeltzer, M.P., Kang, G., Li, C. and Wang, W.C.; (2017); A clinically meaningful fetal hemoglobin threshold for children with sickle cell anemia during hydroxyurea therapy; American Journal of Hematology; 92(12): 1333–1339.
Ghoshal, K. and Bai, S.; (2007); DNA methyltransferases as targets for cancer therapy; Drugs Today (Barc); 43(6): 395–422.
Herrick, J.B.; (1910); Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia; Archive of Internal Medicine; 6: 517–521.
Herrick, J.B.; (2001); Peculiar Elongated and Sickle-shaped Red Blood Corpuscles in a Case of Severe Anemia; Yale Journal of Biology and Medicine; 74: 543–548.
Hoffbrand, A.V., Lewis, M.S. and Tuddenham, E.D.; (2001); Postgraduate Haematology; Oxford University Press; 4th edition: 19.
Ingram, V.M.; (2004); Anecdotal, Historical and Critical Commentaries on Genetics Sickle-Cell Anemia Hemoglobin: The Molecular Biology of the First "Molecular Disease"—The Crucial Importance of Serendipity; Genetics; 167: 11–17.
Li, H., Xie, W. and Gore, E.R.; (2013); Development of phenotypic screening assays for gamma-globin induction using primary human bone marrow day 7 erythroid progenitor cells; Journal of Biomolecular Screen; 18(10): 1212-1222.
Modell, B., Darlison, M.; (2008); Global epidemiology of haemoglobin disorders and derived service indicators; Bulletin World Health Organization; 86(6): 480-487.
Okpala, I.; (2004); The intriguing contribution of white blood cells to sickle cell disease: A red cell disorder; Blood Reviews; 18: 65-73.
Oloopoenia, L., Fredrick, W., Greaves, W. and Adams, R.; (1990); Pneumococcal sepsis and meningitis in adults with sickle cell disease; South Medical Journal; 83: 1002–1004.
Piel, F.B., Patil, A.P., Howes, R.E., Nyangiri, O.A., Gething, P.W., and Williams, T.N.; (2010); Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis; Nature Communication; 1: 104-105.
Ren, J., Singh, B.N., Huang, Q., Li, Z., Gao, Y. and Mishra, P.; (2011); DNA hypermethylation as a chemotherapy target; Cell Signal; 23(7): 1082–1093.
Ren, J., Briones, V., Barbour, S., Yu, W., Han, Y., Terashima, M., and Muegge, K.; (2015); The ATP binding site of the chromatin remodeling homolog Lsh is required for nucleosome density and de novo DNA methylation at repeat sequences; Nucleic Acids Research; 43(3): 1444–1455.
Sankaran, V.G. and Orkin, S.H.; (2013); The switch from fetal to adult hemoglobin; Cold Spring Harbour Perspective Medicine; 3(1): 116-143.
Sankaran, V.G., Xu, J. and Orkin, S.H.; (2010); Advances in the understanding of haemoglobin switching: Review; British Journal of Haematology; 149(2): 191-194.
Sant'Ana, P.G., Araujo, A.M., and Pimenta, C.T.; (2017); Clinical and laboratory profile of patients with sickle cell anemia; Revista Brasileira de Hematologia Hemoterapia; 39(1): 40-45