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

TY - JOUR

T1 - HbA2 levels in normal adults are influenced by two distinct genetic mechanisms

AU - Menzel, Stephan

AU - Garner, Chad

AU - Rooks, Helen

AU - Spector, Tim D.

AU - Thein, Swee Lay

PY - 2013/1

Y1 - 2013/1

N2 - Using a genome-wide association study, we found that common inter-individual differences in haemoglobin A2 (HbA2, alpha 2 delta 2) 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 beta-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.

AB - Using a genome-wide association study, we found that common inter-individual differences in haemoglobin A2 (HbA2, alpha 2 delta 2) 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 beta-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.

KW - haemoglobin regulation

KW - thalassaemias

KW - globin genes

KW - genetics

KW - BETA-THALASSEMIA MUTATIONS

KW - FETAL-HEMOGLOBIN

KW - HBS1L-MYB

KW - REGION

U2 - 10.1111/bjh.12084

DO - 10.1111/bjh.12084

M3 - Article

SN - 0007-1048

VL - 160

SP - 101

EP - 105

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 1

ER -