Factors Associated in Production of Raised Gama Globin Chain in HbE/ ?-Thalassemia ? A Review

HbE/-thalassaemia genotype represent approximately 50 % of all severe -thalassemia worldwide and is the commonest form of thalassemia in many Asian countries, predominantly prevalent in North-Eastern region exhibiting phenotypes that range from severely symptomatic and transfusion-dependent anaemia in early life to a asymptomatic and clinically -silent- condition that is ascertained by chance in middle age. Assay of m-RNA in cell free system clearly shows a deficiency of m-RNAin heterozygous -thalassemic bone marrow. Compensation for defective - chain synthesis by the - chain locus on the unaffected chromosome in -thalassemia heterozygous have been reported. Some genotypic factors have been reported to affect the synthesis of -chain, such as 3-HS1 (+179 C-T) polymorphism, the (AT) xNy (AT) z motif in the 5-HS2 site, the (AT) x (AT) motif in the -540 region of the -globin gene, GATA-1 (26), and heme-regulated initiation factor 2 alpha kinase (HRI). Also genetic variation at three major loci - XmnI-HBG2, HBS1L-MYB intergenicregion on chromosome 6q23 and variation of rs11886868 (T-C) in the BCL11A geneon chromosome 2p16 has account for relatively large proportion (20-50 %) of the phenotypic variation in HbF levels. HbF levels in HbE/-thalassemia, and other thalassemia syndromes, results from increased erythropoietin levels leading to bone marrow expansion, and possibly increased F-cell production, combined with ineffective erythropoiesis giving a survival advantage to F cells. Among the known genetic factors XmnI, DNA sequence variation (C-T) at position -158 upstream of the G globin gene is one of the gene polymorphism that influence HbF production.