Association of -158(C → T) (XmnI) DNA Polymorphism inGγ-Globin Promoter with Delayed Switchover from Fetal to Adult Hemoglobin Synthesis

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Abstract
In this study, the effect of -158(C → T) (XmnI) polymorphism on the synthesis of fetal Hb and its Gγ component during the switchover from fetal to adult Hb was examined using cord blood samples from normal Caucasian term infants. The presence of -158(C→T) mutation was determined by amplification of Gγ- and Aγ-globin gene promoter fragments from the DNA isolated from cord blood samples, followed by XmnI restriction enzyme digestion. The syntheses of fetal and adult Hb in cord blood were measured by [3H]leucine incorporation in globin synthesis, separation of the globin polypeptides by HPLC, and scintillation counting of the fractions. The presence of -158(C→ T) substitution in the Gγ-globin promoter region was positively correlated with elevated synthesis of fetal Hb and itsGγ-globin component in term newborn infants and is associated with delayed switchover from fetal to adult Hb. In addition, analysis of cord blood samples from 100 normal Caucasian French Canadian term infants revealed that the frequency of -158(C → T) substitution inGγ-promoter was 0.32.