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

Abstract

Background: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.

Materials and Methods: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: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).

Conclusion: BCL11A and HBS1L-MYB genes promote induction of fetal haemoglobin in SCA subjects compared with controls recruited for this study.