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Br J Haematol. 2013 Jan;160(1):101-5. doi: 10.1111/bjh.12084. Epub 2012 Oct 9.

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

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Molecular Haematology, James Black Centre, King's College London, 125 Coldharbour Lane, London, UK.


Using a genome-wide association study, we found that common inter-individual differences in haemoglobin A(2) (HbA(2) , α(2) δ(2) ) levels are largely governed by genetic factors (42% of variability). The influence of age (1%) and sex (4%) was small. HbA(2) 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 HbA(2) 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.

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