It has been demonstrated that the persistence of fetal hemoglobin has a marked hereditary character. There are several studies that relate certain genetic polymorphisms or variants with the persistence of fetal hemoglobin in adults and its possible implication in the improvement of symptoms of different types of anemia.
Persistence of fetal hemoglobin
Fetal hemoglobin is the main oxygen transport protein to all parts of the body in the human fetus during the last seven months of development in utero and in the newborn until about 6 months of age, by which time virtually all of it has been replaced by adult hemoglobin. Only about 1% of total adult hemoglobin is fetal hemoglobin.
Functionally, fetal hemoglobin differs from adult hemoglobin in that it is able to bind oxygen with greater affinity, giving the developing fetus better access to oxygen from the mother's bloodstream.
Structurally, fetal hemoglobin is a protein made up of four globins: two alpha-globins and two gamma-globins. During development there is a change in gene expression that causes the gene that produces gamma-globin to stop being expressed and activates the expression of the beta-globin gene, so that adults have hemoglobin that is mostly made up of two alpha-globins and two beta-globins. The transcriptional change of the gene from gamma to beta-globin is commonly referred to as the "fetal to adult hemoglobin switch".
In some individuals the rate of fetal hemoglobin production does not decrease over the years, possibly due to the presence of variants in the BCL11A gene, a gene that acts as a molecular switch in the transition from fetal hemoglobin to adult hemoglobin.
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Genes analyzed
BCL11A
Bibliography
Bauer DE, Orkin SH. Hemoglobin switching's surprise: the versatile transcription factor BCL11A is a master repressor of fetal hemoglobin. Curr Opin Genet Dev. 2015 Aug;33:62-70.
Uda M, Galanello R, Sanna S, Lettre G, Sankaran VG, Chen W, et al. Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia. Proc Natl Acad Sci U S A [Internet]. 2008 Feb 5 [cited 2014 Sep 28];105(5):1620–5.
Liu N, Hargreaves VV, Zhu Q, Kurland JV, Hong J, Kim W, Sher F, et al. Direct Promoter Repression by BCL11A Controls the Fetal to Adult Hemoglobin Switch. Cell. 2018 Apr 5;173(2):430-442.e17.
