Increased levels of hemoglobin A2 (HbA2) are present in most β-thalassemia carriers. The mechanism of this effect is not understood, although the increase may result from transcriptional and posttranscriptional changes. In the present study, we quantitate δ-globin mRNA levels in peripheral-blood-enriched reticulocytes and characterize the variation of δ-mRNA levels in 30 β-thalassemia heterozygotes who individually carry one of the four common Chinese β-thalassemia alleles [codons 41/42 (–TTCT); codon 17 (A→T); IVS-II-654 (C→T); –28 (A→G)]. A sensitive and quantitative competitive reverse-transcriptase polymerase chain reaction method was developed and used to assess the absolute amounts of δ-mRNA transcripts in these peripheral erythroid cells. The results showed a large increase in δ-mRNA amounts in all the carriers examined (72.3 ± 9.0 amol/μg RNA) as compared with those in 12 controls (1.2 ± 0.2 amol/ μg RNA). There was a direct correlation between the δ-mRNA levels and types of β-thalassemia alleles; generally, the δ-mRNA levels are higher in heterozygotes for β⁰-thalassemia mutations than β+-thalassemia mutations. The δ-mRNA levels correlated inversely with hemoglobin and red cell indices but directly with HbA2 levels in heterozygotes of each of the group of β-thalassemia mutations. These results suggest that a greater impairment in β-globin gene expression results in increased transcription of δ-globin gene and in a higher level of HbA2.

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