HbA2 levels in normal adults are influenced by two distinct genetic mechanisms


Correspondence: Swee Lay Thein, Molecular Haematology, King's College London, James Black Centre, 125 Coldharbour Lane, London SE5 9NU, UK.

E-mail: sl.thein@kcl.ac.uk


Using a genome-wide association study, we found that common inter-individual differences in haemoglobin A2 (HbA2, α2δ2) levels are largely governed by genetic factors (42% of variability). The influence of age (1%) and sex (4%) was small. HbA2 levels were influenced by two loci: the HBS1L-MYB locus on chromosome 6q, which has been shown to have pleiotropic effects on other haematological traits; and a second locus surrounding HBB, the gene encoding β-globin. Our results suggest that HbA2 levels in adults are influenced by two different biological processes: one via kinetics of erythropoiesis, and the other, via competition between HBB and HBD activity.