title: The delta-globin RNA transcript level in beta-thalassemia carriers.
abstract: Increased levels of hemoglobin A(2) (HbA(2)) are present in most beta-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 delta-globin mRNA levels in peripheral-blood-enriched reticulocytes and characterize the variation of delta-mRNA levels in 30 beta-thalassemia heterozygotes who individually carry one of the four common Chinese beta-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 delta-mRNA transcripts in these peripheral erythroid cells. The results showed a large increase in delta-mRNA amounts in all the carriers examined (72.3 +/- 9.0 amol/microg RNA) as compared with those in 12 controls (1.2 +/- 0.2 amol/ microg RNA). There was a direct correlation between the delta-mRNA levels and types of beta-thalassemia alleles; generally, the delta-mRNA levels are higher in heterozygotes for beta(0)-thalassemia mutations than beta(+)-thalassemia mutations. The delta-mRNA levels correlated inversely with hemoglobin and red cell indices but directly with HbA(2) levels in heterozygotes of each of the group of beta-thalassemia mutations. These results suggest that a greater impairment in beta-globin gene expression results in increased transcription of delta-globin gene and in a higher level of HbA(2).
authors.affiliation: Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai, China.
authors.forename: S Z
authors.initials: SZ
authors.lastname: Huang
authors.forename: F Y
authors.initials: FY
authors.lastname: Zeng
authors.forename: M J
authors.initials: MJ
authors.lastname: Chen
authors.forename: Z R
authors.initials: ZR
authors.lastname: Ren
authors.forename: M
authors.initials: M
authors.lastname: Shen
authors.forename: G P
authors.initials: GP
authors.lastname: Rodgers
authors.forename: A N
authors.initials: AN
authors.lastname: Schechter
authors.forename: Y T
authors.initials: YT
authors.lastname: Zeng
mesh_terms: D044466:Asian People / Q000235:genetics*; D002648:Child; D003062:Codon; D006580:Genetic Carrier Screening; D005914:Globins / Q000235:genetics*; D006801:Humans; D016014:Linear Models; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism*; D012156:Reticulocytes / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D003062:Codon; D012333:RNA, Messenger; D005914:Globins