Concordant hbf response to hydroxyurea (HU) in siblings with sickle cell anemia

M. H. Steinberg, F. Barton, A. Kutlar, M. Koshy, S. K. Ballas, O. Castro

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


HbF level and the HbF response to HU vary widely in HbSS. Both are controlled by genetic elements linked and unlinked to the β-like globin gene cluster. We studied 14 adult sib pairs and 3 families of 3 siblings with HbSS to see if sibs had discordant or concordant increments in HbF during HU treatment. Intraclass correlation coefficients (r) between sibs in WBC count, reticulocytes, MCV, hemoglobin and HbF are shown in the table: WBC Relics MCV Hb HbF Pre-HU 0.02 -0.55 0.52 0.19 0.67 (») PosI-HU 0.52 0.56 0.45 0.02 0.60 (%) Change 0.15 -0.66 0.24 0.50 0.43 (g/dL) (p<0.05: 'p<O.OD There was a high, positive correlation between sibs in HbF and MCV, both before and after HU treatment. Using regression between sibs of change from pre to post H U levels, adjusting for baseline levels, there is a possible HU-mediated effect (P<0.05) detected in MCV, Hb and HbF, bul not in WBC or reticulocyte counts. Siblings of the same or different sexes had similar results suggesting that an X chromosome-linked locus does not affect the HbF response to HU. In 11 of 12 families with data available, siblings had identical βglobin gene cluster haplotypes making them, in effect, monozygotic in their β-globin gene cluster. This suggests that one determinant of the HbF response to HU may be linked to the β-globin gene cluster. Previously, we found that functionally important polymorphisms in about 65 kb of the β-globin gene cluster were always haplotype-linked suggesting that variations in these particular elements are uncommon mechanisms of HbF modulation in HbSS. Our sib studies suggest that a renewed search for regulatory elements linked to the β-globin gene may identify predictors of the HbF response to HU and new targets for pharmacologie or gene therapy.

Original languageEnglish (US)
Pages (from-to)9a
Issue number11 PART I
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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