Association of BCL11A and HBS1L-MYB Polymorphisms in Sickle Cell Anaemia Subjects of Different Age Groups in Nigeria

Abstract

Haematological features and clinical severity of Sickle Cell Anaemia (SCA) are influenced by age, gender, genetic and community factors. BCL11A is cytogenetically located on short arm of chromosome 2 at position 16.1 while it is located at base pair 60,451,167 to 60,553,498 on chromosome 2 at the molecular level. Polymorphisms in the HBS1L-MYB Intergenic region were associated with F-cell levels and accounted for 19.4% of the F-cell variance in normal Europeans. This study highlights possible effects of age in Haemoglobin F Induction through possible association of BCL11A and HBS1L-MYB genes polymorphism in SCA Subjects population in Oshogbo metropolis. Thirty – Six SCA subjects were recruited with ages ranging between 1 and 40years divided into five groups of eight subjects each except age ranges 21 to 25 and 25 to 40 years which were six subjects each, while ten haemoglobin A subjects served as control for all age ranges. Red Cell indices and gene analysis such as HCT, RBC Count, Haemoglobin concentration, Hb F level, BCL11A and HBS1L-MYB genes were studied using standard methods. Results shows no statistically significant difference in fetal haemoglobin between control and subjects (P>0.05). There was a statistical decrease in haemoglobin level in the test subjects compared to controls. Also, the HBS1L-MYB protein expression was not significantly different in Haemoglobin A subjects and the SCA subjects, but there was a statistically significant decrease in BCL11A gene expression in SCA Subjects compared to Haemoglobin A Subjects (P<0.05). A statistically significant decrease in BCL11A gene expression was obtained in ages 16 to 20 and 21 to 40years age groups (p<0.05). There was a positive correlation between Fetal Haemoglobin and haematocrit and haemoglobin levels (r=0.04341, p=0.2227); (r=0.01705, p=0.4479), respectively. The correlation between Fetal haemoglobin and BCL11A and HBS1L-MYB showed statistically significant negative correlations (r= - 0.1220, p=0.0368), r= - 0.1260, p=0.0336 respectively). Conclusively, BCL11A and HBS1L-MYB genes promote induction of fetal haemoglobin in SCA subjects compared with controls recruited for this study.