Association ofXmnI Polymorphism and Hemoglobin E Haplotypes on Postnatal Gamma Globin Gene Expression in Homozygous Hemoglobin E

Abstract

Background and Objectives. To explore the role ofcis-regulatory sequences within theβglobin gene cluster at chromosome 11 on humanγglobin gene expression related to Hb E allele, we analyze baseline hematological data and Hb F values together withβglobin haplotypes in homozygous Hb E.Patients and Methods. 80 individuals with molecularly confirmed homozygous Hb E were analyzed for theβglobin haplotypes andXmnI polymorphism using PCR-RFLPs. 74 individuals with complete laboratory data were further studied for association analyses.Results. Eight differentβglobin haplotypes were found linked to Hb E alleles; three major haplotypes were (a) (III), (b) (V), and (c) (IV) accounting for 94% of Hb E chromosomes. A new haplotype (Th-1) was identified and most likely converted from the major ones. The majority of individuals had Hb F < 5%; only 10.8% of homozygous Hb E had high Hb F (average 10.5%, range 5.8–14.3%). No association was found on a specific haplotype orXmnI in these individuals with high Hb F, measured by alkaline denaturation. Conclusion. The cis-regulation ofγglobin gene expression might not be apparent under a milder condition with lesser globin imbalance such as homozygous Hb E.