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In this study, the effect of -158 (C-->T) (XmnI) polymorphism on the synthesis of fetal Hb and its G gamma 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 G gamma and A gamma-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 G gamma-globin promoter region was positively correlated with elevated synthesis of fetal Hb and its G gamma-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 in G gamma-promoter was 0.32.
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