ASSOCIATION BETWEEN GLOBAL DNA METHYLATION PATTERN

ABSTRACT

Sickle cell disease (SCD) is one of the most prevalent hemoglobinopathies worldwide. Hydroxyurea, L-glutamine and crizanlizumab have shown promising results in SCD therapy. DNA methylation mechanisms have been implicated in the conversion of HbF to adult haemoglobin and the presences of HbF in Sickle Cell disease has been reported as good prognosis. The objective of this study was to determine the activities of DNA methyltransferase 1 in sickle cell subjects. 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. DNA methyltransferase 1 was determined using ELISA kits from Elabscience Biotechnology, Wuhan, China. Complete blood count was analysed using 3 part sysmex auto-analyzer Kobe, Japan. The results showed that DNA methyltransferase 1 activity in sickle cell subjects (2.347±0.2472) was significantly low (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. SCD subjects on hydroxyurea (2.342±0.8018) had a significantly lower (p<0.0001) DNA methyltransferase 1 activity when compared to 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). Furthermore, leg ulcer (81.67%), acute chest syndrome (80%) and vaso-occulusive crises (76.67%), accounted for the common complication in sickle cell subjects recruited for this study. Also most SCD subjects were on folic acid (98.33%) supplement and 11.67% were on hydroxyurea, 10% were on Lglutamine, 6.67% were on Crizanlizumab and 18.33% were on Voxelotor.In conclusion, DNA methyltransferase 1 activity low in sickle cell subjects, especially in subjects on hydroxyurea, Crizanlizumab and Voxelotor. Which may indicate that target DNA methylation with other known hypomethylating agent in sickle cell patients maybe a viable therapeutic option.