The genetics of hemoglobin A2 regulation in sickle cell anemia. Issue 11 (4th August 2014)

• Record Type: Journal Article
• Authors: Griffin, Paula J.; Sebastiani, Paola; Edward, Heather; Baldwin, Clinton T.; Gladwin, Mark T.; Gordeuk, Victor R.; Chui, David H.K.; Steinberg, Martin H.
• Is Part Of: American journal of hematology. Volume 89:Issue 11(2014:Nov.)
• Page Start: 1019
• Page End: 1023
• Publication Date: 2014-08-04
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.23811
• Languages: English
• ISSNs: 0361-8609

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Hemoglobin A₂, a tetramer of α‐ and δ‐globin chains, comprises less than 3% of total hemoglobin in normal adults. In northern Europeans, single nucleotide polymorphisms (SNPs) in the <italic>HBS1L‐MYB</italic> locus on chromosome 6q and the <italic>HBB</italic> cluster on chromosome 11p were associated with HbA₂ levels_. We examined the genetic basis of HbA₂ variability in sickle cell anemia using genome‐wide association studies. HbA₂ levels were associated with SNPs in the <italic>HBS1L‐MYB</italic> interval and SNPs in <italic>BCL11A</italic>. These effects are mediated by the association of these loci with γ‐globin gene expression and fetal hemoglobin (HbF) levels. The association of polymorphisms downstream of the β‐globin gene (<italic>HBB</italic>) cluster on chromosome 11 with HbA₂ was not mediated by HbF. In sickle cell anemia, levels of HbA₂ appear to be modulated by trans‐acting genes that affect <italic>HBG</italic> expression and perhaps also elements within the β‐globin gene cluster. HbA₂ is expressed pancellularly and can inhibit HbS polymerization. It remains to be seen if genetic regulators of HbA₂ can be exploited for therapeutic purposes. Am. J. Hematol. 89:1019–1023, 2014. © 2014 Wiley Periodicals, Inc.</p> </abstract>